Proteopedia - User contributions [en]

Globular Proteins

2012-11-06T19:55:53Z

Karl Oberholser:

Globular proteins have a 3D molecular structure that has a shape that is anywhere from a sphere to a cigar. Usually the structure of a globular protein is divided into three or four levels. The primary structure is simply the sequence of amino acids forming the peptide chain. The peptide chain can be folded in an ordered and repetitive fashion, and the structures with ordered and repetitive conformations are called [[Secondary_structure|secondary structures]]. [[Helices_in_Proteins|Helices]], [[Sheets in Proteins|β-sheets]] and [[Turns in Proteins|turns]] are three important types of secondary structures. Turns are classified as a secondary structure even though their structures are ordered but not repetitive. The tertiary structure is the overall 3D structure of a globular protein and is produced by folding the helices and sheets upon themselves with turns and [[Loops in Proteins|loops]] forming the folds. Non-covalent molecular attractions are important forces in maintaining the folded conformation of a globular protein. For the most part, these attractions are between the atoms of the side chains but can be between the side chains and a bound ligand. Hydrogen bonds between back bone atoms are important in maintaining secondary structures, and those between side chains are involved in maintaining the tertiary structure. Examples of finding and visualizing both types in globular proteins are at [[Hydrogen bonds |hydrogen bonds]]. The attractive forces of [[Salt_bridges |salt bridges]] are important in maintaining some tertiary structures, but they also can be involved in the binding of ligands. The Disulfide bond is the one type of covalent bond that can play an important role in maintaining the tertiary structure as well as connecting two or more peptide chains together. Links to sites having structures that illustrate disulfide bonds are at [[Cystine]]. Some globular proteins have a quaternary structure, and it is formed when two or more globular protein molecules (monomer) join together and form a multimeric unit. [[Hemoglobin]] is a good example of a protein that has a quarternary structure.

The tertiary structure of many globular proteins can be characterized by the number of layers of peptide backbone which are present and the attractive forces which are generated by these layers.<ref name='Garret'>Biochemistry, 4th ed., R. H. Garrett & C. M. Grisham, Thomson/Brooks/Cole, pages 167-170.</ref> Other important characteristics in the absence of backbone layers are the presence of disulfice bonds, of chelated metal ions or of intrinsically unstructured segments <ref name='Garret'/>. The objective of this page is to introduce the tertiary structures of globular proteins by illustrating these characteristics of globular proteins.

== Layers of Backbone Present in the Structure ==

Layers of backbone in the core of the structure is a feature that many, but not all, globular proteins have. The number of layers and their location vary for different proteins, but in all of these proteins the hydrophobic forces between the layers play a major role in maintaining the tertiary structure.
<StructureSection load='1a7v' size='500' frame='true' align='right' scene ='Globular_Proteins/Two_layers/3' caption='' >__NOTOC__
=== Two Layers ===
The ribbons representing the backbones show the two layers of α-helices. The <scene name='Globular_Proteins/Two_layers_phobic/1'>hydrophobic side chains</scene> are shown in ball and stick with one layer colored green and the other cyan. Notice that these side chains are mostly located between the layers and that few are on the exterior of the molecule. View the <scene name='Globular_Proteins/Two_layers_vdw_contact/1'>points of hydrophobic attraction</scene> between the two layers. The <scene name='Globular_Proteins/Two_layers_hbond_contact/2'>hydrogen bonds</scene> between the layers are only on the edges. The <scene name='Globular_Proteins/Two_layers_polar/1'>polar residues</scene> are now ball & stick, and they tend to be on the surface of the molecule where they can associate with <scene name='Globular_Proteins/Two_layers_water/1'>water</scene>. More clearly see polar groups on the surface by <scene name='Globular_Proteins/Two_layers_polar_rot/1'>rotating structure</scene> so that axis of helix aligns with z-axis, compare this scene with a similarly aligned display of the hydrophobic side chains.

=== Three Layers ===
Load the <scene name='Globular_Proteins/Three_layers/3'>structure</scene> and rotate it to observe the three layers. Hopefully you positioned it similar to these <scene name='Globular_Proteins/Three_layers_positioned/2'>three colored layers</scene>. Show the hydrophobic residues in <scene name='Globular_Proteins/Three_layers_phobic/1'>ball and stick</scene>. With the CyanDark layer being the middle layer most of its side chains are nonpolar. The hydrophobic side chains are again nearly all located between the layers. Toggling spin off and rotating the structure to align the helical axis with the z-axis gives an even better view of this effect. Display the polar residues in <scene name='Globular_Proteins/Three_layers_polar/1'>ball and stick</scene>. The polar side chains are almost exclusively on the surface of the molecule, and therefore the middle CyanDark layer has very few polar side chains.

=== Circular Layers ===
Load the <scene name='Globular_Proteins/Circular_layers/1'>structure</scene>. The circular layers formed by the β-sheet barrel (yellow) and α-helix barrel are clearly seen in this view, giving what would appear to be two layers. <scene name='Globular_Proteins/Circular_layers_phobic/1'>Next scene</scene> shows that hydrophobic residues occupy the central circular cavity as well as the space between the two circular layers. With this being the case one could say that the isomerase had four layers of backbone. <scene name='Globular_Proteins/Circular_layers_polar/1'>Display polar residues</scene>. As the structure rotates one can see that most of the polar residues are on the surface, but there are few within the central cavity and between the two circular layers. The β-sheet of the barrel is parallel because after forming a strand of the sheet the peptide chain loops out, forms an α-helix and then loops back to form another strand of the sheet running in the same direction as the previous strand and, thereby, making the sheet parallel.

=== Five Layers ===
Load <scene name='Globular_Proteins/Five_layers/3'>structure</scene>. Rotate the structure and attempt to identify the five layers.
The five layers are <scene name='Globular_Proteins/Five_layers_identified/2'>identified</scene> in colors Brown through Red. Display<scene name='Globular_Proteins/Five_layers_phobic/1'> hydrophobic residues</scene>; it is not as obvious as with the previous proteins, but as the structure rotates one can see that most of the spheres are in the interior between the layers. Looking at the <scene name='Globular_Proteins/Five_layers_polar/1'>polar residues</scene>, as it rotates one can observe more spheres on the edges of the structure than were seen in the previous scene.

=== Other Examples ===
Other examples of protein having the characteristic of layered backbones will be divided into three categories - predominately α-helix, predominately β-sheets and mixed α-helix and β-sheets.

==== Predominately Helices ====
The peptides in this class have a high contain of α-helix and because of the loops and turns which are present the α-helical strands will be antiparallel with respect to their adjacent strands.

* <scene name='Globular_Proteins/Anti_helix_erythrin2/1'>Myohemerythrin</scene> - transports oxygen in some lower animals. Notice that the change in direction produced by the turns and loops creates the antiparallel conformation.
* <scene name='Globular_Proteins/Human_gh/1'>Human growth human</scene> - small peptide in humans that stimulates cell division and growth in select tissues.
* <scene name='Globular_Proteins/Myoglobin2/1'>Myoglobin</scene> - stores molecular oxygen in muscle tissue. Structure of [[myoglobin]] is more complex, but again the striking feature is the antiparallel α-helices.
* <scene name='Globular_Proteins/Gluccanase/1'>Endoglucanase A</scene> - an α-helical barrel. Catalytic core of 1,4-beta glucan-glucanohydrolase from ''Clostridium thermocellum''.
* <scene name='Globular_Proteins/Leu_rich/1'>Leucin-rich repeat variant</scene> - a novel structural motif. It is an iron-sulfur protein from ''Azotobacter vinelandii'' and involved in redox reactions of nitrogen fixation.

==== Predominately β-Sheets ====
* <scene name='Globular_Proteins/St_inhibitor/1'>Soybean trypsin inhibitor</scene> - As its name implies this protein inhibits the enzyme trypsin, and this inhibitory effect must be deactivated in the process of preparing soybeans for use in animal feed, so that the proteins in soybeans are hydrolyzed by trypsin. This protein is an example of the antiparallel β-barrel because the circular antiparallel sheet is barrel shaped. It is not as clearly defined as the parallel β-barrel, described above, but it is more common. You can look through the barrel whenever one of the open ends rotates to face the screen. An outer layer of α-helices is not present like it is in the parallel β-barrel, so the side chains projecting from the outer surface of the sheet are polar and make contact with water.
* <scene name='Globular_Proteins/Agguluttinin/1'>Aggluttinin</scene> - a mannose specific lectin from the bulb of snowdrop. A lectin is a protein that binds oligsaccharides and glycoproteins and is involved in cell-cell recognition. Notice the prism like shape that is formed by the β-sheets.
* <scene name='Globular_Proteins/Rieske/1'>Rieske protein</scene> - water soluble fragment (head) of the iron-sulfur protein from bovine heart. It is a component of Complex III of the mitochondrial respiratory chain.
* <scene name='Globular_Proteins/Lectin_r_s/1'>Lectin</scene> - from ''R. solanacearum''. It is an example of a protein having a quaternary structure, in this case it is trimeric - <scene name='Globular_Proteins/Lectin_r_s2/1'>three subunits</scene>. This type of structure is called a six-bladed propellor or β-propellor. Each subunit contributes two propellors.

==== Mixed helices and β-Sheets ====
* <scene name='Globular_Proteins/Tmvp2/1'>Tobacco mosaic virus protein</scene> - forms the capsid of the virus. Again the α-helices, loops and turns are prominent features, and the α-helices are antiparallel.
* <scene name='Globular_Proteins/Porin/1'>Matrix porin</scene> - integral protein from the outer membrane of ''E. coli''. Since the barrel structure is inserted into the interior of the membrane, the outer surface that contacts the membrane must be largely <scene name='Globular_Proteins/Porin_phobic/1'>hydrophobic</scene>, but the ends, which contact water, and much of the interior is <scene name='Globular_Proteins/Porin_polar/1'>polar</scene>. <scene name='Globular_Proteins/Porin_polar_phobic/1'>Both</scene> shown together.
* <scene name='Globular_Proteins/Concan/1'>Concanavalin</scene> - Example of another lectin. Notice that the tertiary structures of the three lectins are different revealing that the structures can be different but yet have the same general function. There are two antiparallel β-sheets with the hydrophobic sides of the sheets facing each other. They are interlocking β-Sheets or have Greek Key Topology, ''i.e.'' after laying down a strand in a sheet, often the peptide chain loops over to the other sheet and lays down a strand in that sheet.
* <scene name='Globular_Proteins/Crystallin/1'>Gamma-Crystallin</scene> - A protein that is a component of the eye lense. This protein is another example of interlocking β-sheet, two of the Greek key bilayers are connected by a looping peptide segment.
* <scene name='Globular_Proteins/Protein_l9/1'>Ribosomal protein L9</scene> - from B. stearothermophillus, a prokayote. The length of the long α-helix is invariant with other prokayotic L9 proteins.
* <scene name='Globular_Proteins/Flavodxin/1'>Flavodoxin</scene> - This type of structure is also called doubly wound parallel β-sheet because of the loops of α-helices on both sides of the sheet. In some cases these doubly wound sheets contain a few antiparallel strands forming a mixed β-sheet. Can you find the three layers of backbone in these doubly wound sheets contain?
* <scene name='Globular_Proteins/Pg_mutase/1'>Phosphoglycerate mutase</scene> - There is one antiparallel strand in the sheet, and the double winding is more extensive.
* <scene name='Globular_Proteins/Rnase/1'>Ribonuclease H</scene> - endoribonuclease from ''E. coli'' that cleaves the RNA strand of a RNA:DNA duplex and produces oligonucleotides. This activity is involved in bacterial replication and required for retrovirial infection. The ''E. coli'' enzyme is homologous with retrovirial proteins.
* <scene name='Globular_Proteins/Ruva/1'>RuvA protein</scene> - ''E. coli'' protein that binds DNA along with RuvB, a helicase, and both are involved in DNA repair, SOS response and DNA recombination. Residues 143-156 are misssing.
* <scene name='Globular_Proteins/Horseshoe/1'>Porcine ribonuclease inhibitor</scene> - contains leucine-rich repeats.

</StructureSection>
<table width='500' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Tertiary Structures of Examples'''<scene name='Globular_Proteins/Two_layers/2'> (Initial scene)</scene></center></td></tr></table>
{{Clear}}
== Other Characteristics ==
Disulfide bonds and metal ion chelates can stabilize the tertiary structure in the absence of well organized layers which generate hydrophobic attractions. Some proteins are small in size and therefore do not have large amounts of backbone that can be organized into layers. Others have significant backbone, but the layers are not well organized and therefore are non-stabilizing. The attractions formed by metal ions chelates or disulfide bonds in these proteins are as important or more so than the hydrophobic interactions of the organized layers. Examples of both types of bonds will be given.

Some proteins or peptide segments are [[Intrinsically_Disordered_Protein |intrinsically disordered]] (unstructured). Whether a complete protein or a protein segment since they are disordered, they can not be crystallized for x-ray crystallographic study. However, when these peptides or peptide segments bind to other proteins they become ordered segments, and can be crystallized along with the binding protein for x-ray crystallographic study. When these peptides bind to other proteins, since their conformations are extended and not compact, the binding occurs over relatively large surface areas of the binding proteins. Examples given below illustrate the extended conformations of the peptide segments as well as the large binding surface. When viewing the unstructured peptides as unbound segments, realize that the conformation which is being displayed is not a disordered conformation but is the conformation of the bound segments with the structure of the binding protein being hidden. If the peptides or peptide fragments were actually free and unbound, since they are unordered, the individual molecules would have a range of conformations and not just one.
<StructureSection load='2ben' size='500' side='right' caption='' scene='Globular_Proteins/Insulin1/1'>__NOTOC__

=== Disulfide-Rich Proteins ===
* <scene name='Globular_Proteins/Insulin1/1'>Insulin</scene> - Among its functions is the regulation of glucose uptake by cells. The small peptide contains A and B chains that are connected by disulfide bonds, and the tertiary structure of the A chain is also held in place by a disulfide bond.
* <scene name='Globular_Proteins/Crambin/1'>Crambin</scene> - Plant seed peptide. Small single chain peptide with no significant backbone layers but has disulfide bonds to stabilize the tertiary structure. Disulfide bonds, also, have an important role of keeping the relatively high proportion of loops in place.
* <scene name='Globular_Proteins/Pholipase2/1'>Phospholipase A2</scene> - Part of a class of hydrolases that degrade glycerophospholipids. This one specifically hydrolyzes the second acyl group on the glycero group. This example is larger than the other two, but it still does not have well organized backbone layers in part due to the extensive turns and loops.

=== Metal-Rich Proteins ===
* <scene name='Globular_Proteins/Hp_iron/1'>High-potential iron protein</scene> - An iron-sulfur protein that has an unusually high redox potential. The Fe's of the iron-sulfur (yellow) center are complexed with the side chains of Cys which are part of different loops of the peptide. Without a large number of hydrophobic groups to form attractions these sulfur-metal bonds are important in maintaining the tertiary structure.
* <scene name='Globular_Proteins/Ferredoxin/1'>Ferredoxin</scene> - Protein with two iron-sulfur centers; the major function of iron-sulfur proteins is involvement in redox reaction. Both iron-sulfur centers are complexed with the side chains of Cys and aid in maintaining the tertiary structure.

=== Intrinsically Unstructured Proteins ===
* <scene name='Globular_Proteins/Lef-1/1'>LEF-1</scene>, lymphoid enhancer-binding factor 1. LEF-1 is missing residues 26-47, and these residues are most likely missing because they form an unordered segment. Fill in this gap in your mind's eye, and you will see the large <scene name='Globular_Proteins/Lef-1_2/1'>surface area</scene> with which LEF-1 (yellow) binds to β-catenin. Apparently the binding strength of the missing segment is such that it is not converted to an ordered segment. You may notice that residues 550-561 of β-catenin are also missing, again an unordered segment.
* <scene name='Globular_Proteins/Snap2/2'>SNAP-25</scene> - Domain N2 of synaptosomal-associated protein 25 (blue) from human bound to botulinum neurotoxin type A light chain (botox) from ''C. botulinum''. <scene name='Globular_Proteins/Snap/2'>Domain N2</scene> shown unbound but having the same conformation as the bound peptide.
* <scene name='Globular_Proteins/Sara_sbd2/1'>SARA SBD</scene> - SMAD Anchor for Receptor Activation SMAD-Binding Domain bound to SMAD2 MH2 domain. SARA SBD is the domain of the receptor that binds SMAD, and thereby activates the transforming growth factor-beta signaling pathway. <scene name='Globular_Proteins/Sara_sbd/2'>SMAD-binding domain</scene> shown unbound and displayed as cartoon but having the same conformation as the bound peptide.
* <scene name='Globular_Proteins/Hif-1alpha2/2'>HIF-1alpha</scene> - Hypoxia-inducing factor 1α (C-terminal activation domain) bound to transcription activation zinc finger domain of CREB-binding protein. <scene name='Globular_Proteins/Hif-1alpha/2'>HIF</scene> shown unbound and displayed as cartoon but having the same conformation as the bound peptide. The data of this model was generated by NMR analysis of an aqueous solution of the peptides, and the analysis is rapid enough to distinguish the vibrations of the peptides so that more than one model is produced. It is possible to animate these multiple model and simulate the vibrations of the peptides. Notice that the vibrations are the greatest in the molecules where the attractive forces are the weakest. Animate peptides: Unbound <scene name='Globular_Proteins/Hif-1alpha/1'>HIF</scene>; Bound <scene name='Globular_Proteins/Hif-1alpha2/1'>HIF</scene>
* <scene name='Globular_Proteins/P27-cdk2/1'>p27-Cdk2-Cyclin A</scene> - Cyclin-dependent kinase 2 bound to its activator cyclin A and both bound with a fragment (blue) of p27 which is a kinase inhibitor. Cyclin-dependent kinases have an important role in moving the cell from one phase of the cell cycle to another. <scene name='Globular_Proteins/P27-cdk2-2/2'>p27</scene> shown unbound but having the same conformation as the bound peptide.
* <scene name='Globular_Proteins/P27_30-35/1'>p27 (30-35)-Cdk2-Cyclin A</scene> - different data file than the one above containing a smaller fragment of p27 bound to complex. <scene name='Globular_Proteins/P27_30-35-2/1'>p27</scene> shown unbound but having the same conformation as the bound peptide. Compare the conformation of this small fragment to that of the yellow colored fragment shown unbound above. Since the binding site is the same in both models when the peptides bind, regardless of the length, the peptides generate the same conformation.
</StructureSection>

==References==
{{Reflist}}

Globular Proteins

2012-11-06T19:16:05Z

Karl Oberholser:

Globular proteins have a 3D molecular structure that has a shape that is anywhere from a sphere to a cigar. Usually the structure of a globular protein is divided into three or four levels. The primary structure is simply the sequence of amino acids forming the peptide chain. The peptide chain can be folded in an ordered and repetitive fashion, and the structures with ordered and repetitive conformations are called [[Secondary_structure|secondary structures]]. [[Helices_in_Proteins|Helices]], [[Sheets in Proteins|β-sheets]] and [[Turns in Proteins|turns]] are three important types of secondary structures. Turns are classified as a secondary structure even though their structures are ordered but not repetitive. The tertiary structure is the overall 3D structure of a globular protein and is produced by folding the helices and sheets upon themselves with turns and [[Loops in Proteins|loops]] forming the folds. Non-covalent molecular attractions are important forces in maintaining the folded conformation of a globular protein. For the most part, these attractions are between the atoms of the side chains but can be between the side chains and a bound ligand. Hydrogen bonds between back bone atoms are important in maintaining secondary structures, and those between side chains are involved in maintaining the tertiary structure. Examples of finding and visualizing both types in globular proteins are at [[Hydrogen bonds |hydrogen bonds]]. The attractive forces of [[Salt_bridges |salt bridges]] are important in maintaining some tertiary structures, but they also can be involved in the binding of ligands. The Disulfide bond is the one type of covalent bond that can play an important role in maintaining the tertiary structure as well as connecting two or more peptide chains together. Links to sites having structures that illustrate disulfide bonds are at [[Cystine]]. Some globular proteins have a quaternary structure, and it is formed when two or more globular protein molecules (monomer) join together and form a multimeric unit. [[Hemoglobin]] is a good example of a protein that has a quarternary structure.

The tertiary structure of many globular proteins can be characterized by the number of layers of peptide backbone which are present and the attractive forces which are generated by these layers.<ref name='Garret'>Biochemistry, 4th ed., R. H. Garrett & C. M. Grisham, Thomson/Brooks/Cole, pages 167-170.</ref> Other important characteristics in the absence of backbone layers are the presence of disulfice bonds, of chelated metal ions or of intrinsically unstructured segments <ref name='Garret'/>. The objective of this page is to introduce the tertiary structures of globular proteins by illustrating these characteristics of globular proteins.

== Layers of Backbone Present in the Structure ==

Layers of backbone in the core of the structure is a feature that many, but not all, globular proteins have. The number of layers and their location vary for different proteins, but in all of these proteins the hydrophobic forces between the layers play a major role in maintaining the tertiary structure.
<StructureSection load='1a7v' size='500' frame='true' align='right' scene ='Globular_Proteins/Two_layers/2' caption='' >__NOTOC__
=== Two Layers ===
The ribbons representing the backbones show the two layers of α-helices. The <scene name='Globular_Proteins/Two_layers_phobic/1'>hydrophobic side chains</scene> are shown in ball and stick with one layer colored green and the other cyan. Notice that these side chains are mostly located between the layers and that few are on the exterior of the molecule. View the <scene name='Globular_Proteins/Two_layers_vdw_contact/1'>points of hydrophobic attraction</scene> between the two layers. The <scene name='Globular_Proteins/Two_layers_hbond_contact/1'>hydrogen bonds</scene> between the layers are only on the edges. The <scene name='Globular_Proteins/Two_layers_polar/1'>polar residues</scene> are now ball & stick, and they tend to be on the surface of the molecule where they can associate with <scene name='Globular_Proteins/Two_layers_water/1'>water</scene>. More clearly see polar groups on the surface by <scene name='Globular_Proteins/Two_layers_polar_rot/1'>rotating structure</scene> so that axis of helix aligns with z-axis, compare this scene with a similarly aligned display of the hydrophobic side chains.

=== Three Layers ===
Load the <scene name='Globular_Proteins/Three_layers/3'>structure</scene> and rotate it to observe the three layers. Hopefully you positioned it similar to these <scene name='Globular_Proteins/Three_layers_positioned/2'>three colored layers</scene>. Show the hydrophobic residues in <scene name='Globular_Proteins/Three_layers_phobic/1'>ball and stick</scene>. With the CyanDark layer being the middle layer most of its side chains are nonpolar. The hydrophobic side chains are again nearly all located between the layers. Toggling spin off and rotating the structure to align the helical axis with the z-axis gives an even better view of this effect. Display the polar residues in <scene name='Globular_Proteins/Three_layers_polar/1'>ball and stick</scene>. The polar side chains are almost exclusively on the surface of the molecule, and therefore the middle CyanDark layer has very few polar side chains.

=== Circular Layers ===
Load the <scene name='Globular_Proteins/Circular_layers/1'>structure</scene>. The circular layers formed by the β-sheet barrel (yellow) and α-helix barrel are clearly seen in this view, giving what would appear to be two layers. <scene name='Globular_Proteins/Circular_layers_phobic/1'>Next scene</scene> shows that hydrophobic residues occupy the central circular cavity as well as the space between the two circular layers. With this being the case one could say that the isomerase had four layers of backbone. <scene name='Globular_Proteins/Circular_layers_polar/1'>Display polar residues</scene>. As the structure rotates one can see that most of the polar residues are on the surface, but there are few within the central cavity and between the two circular layers. The β-sheet of the barrel is parallel because after forming a strand of the sheet the peptide chain loops out, forms an α-helix and then loops back to form another strand of the sheet running in the same direction as the previous strand and, thereby, making the sheet parallel.

=== Five Layers ===
Load <scene name='Globular_Proteins/Five_layers/3'>structure</scene>. Rotate the structure and attempt to identify the five layers.
The five layers are <scene name='Globular_Proteins/Five_layers_identified/2'>identified</scene> in colors Brown through Red. Display<scene name='Globular_Proteins/Five_layers_phobic/1'> hydrophobic residues</scene>; it is not as obvious as with the previous proteins, but as the structure rotates one can see that most of the spheres are in the interior between the layers. Looking at the <scene name='Globular_Proteins/Five_layers_polar/1'>polar residues</scene>, as it rotates one can observe more spheres on the edges of the structure than were seen in the previous scene.

=== Other Examples ===
Other examples of protein having the characteristic of layered backbones will be divided into three categories - predominately α-helix, predominately β-sheets and mixed α-helix and β-sheets.

==== Predominately Helices ====
The peptides in this class have a high contain of α-helix and because of the loops and turns which are present the α-helical strands will be antiparallel with respect to their adjacent strands.

* <scene name='Globular_Proteins/Anti_helix_erythrin2/1'>Myohemerythrin</scene> - transports oxygen in some lower animals. Notice that the change in direction produced by the turns and loops creates the antiparallel conformation.
* <scene name='Globular_Proteins/Human_gh/1'>Human growth human</scene> - small peptide in humans that stimulates cell division and growth in select tissues.
* <scene name='Globular_Proteins/Myoglobin2/1'>Myoglobin</scene> - stores molecular oxygen in muscle tissue. Structure of [[myoglobin]] is more complex, but again the striking feature is the antiparallel α-helices.
* <scene name='Globular_Proteins/Gluccanase/1'>Endoglucanase A</scene> - an α-helical barrel. Catalytic core of 1,4-beta glucan-glucanohydrolase from ''Clostridium thermocellum''.
* <scene name='Globular_Proteins/Leu_rich/1'>Leucin-rich repeat variant</scene> - a novel structural motif. It is an iron-sulfur protein from ''Azotobacter vinelandii'' and involved in redox reactions of nitrogen fixation.

==== Predominately β-Sheets ====
* <scene name='Globular_Proteins/St_inhibitor/1'>Soybean trypsin inhibitor</scene> - As its name implies this protein inhibits the enzyme trypsin, and this inhibitory effect must be deactivated in the process of preparing soybeans for use in animal feed, so that the proteins in soybeans are hydrolyzed by trypsin. This protein is an example of the antiparallel β-barrel because the circular antiparallel sheet is barrel shaped. It is not as clearly defined as the parallel β-barrel, described above, but it is more common. You can look through the barrel whenever one of the open ends rotates to face the screen. An outer layer of α-helices is not present like it is in the parallel β-barrel, so the side chains projecting from the outer surface of the sheet are polar and make contact with water.
* <scene name='Globular_Proteins/Agguluttinin/1'>Aggluttinin</scene> - a mannose specific lectin from the bulb of snowdrop. A lectin is a protein that binds oligsaccharides and glycoproteins and is involved in cell-cell recognition. Notice the prism like shape that is formed by the β-sheets.
* <scene name='Globular_Proteins/Rieske/1'>Rieske protein</scene> - water soluble fragment (head) of the iron-sulfur protein from bovine heart. It is a component of Complex III of the mitochondrial respiratory chain.
* <scene name='Globular_Proteins/Lectin_r_s/1'>Lectin</scene> - from ''R. solanacearum''. It is an example of a protein having a quaternary structure, in this case it is trimeric - <scene name='Globular_Proteins/Lectin_r_s2/1'>three subunits</scene>. This type of structure is called a six-bladed propellor or β-propellor. Each subunit contributes two propellors.

==== Mixed helices and β-Sheets ====
* <scene name='Globular_Proteins/Tmvp2/1'>Tobacco mosaic virus protein</scene> - forms the capsid of the virus. Again the α-helices, loops and turns are prominent features, and the α-helices are antiparallel.
* <scene name='Globular_Proteins/Porin/1'>Matrix porin</scene> - integral protein from the outer membrane of ''E. coli''. Since the barrel structure is inserted into the interior of the membrane, the outer surface that contacts the membrane must be largely <scene name='Globular_Proteins/Porin_phobic/1'>hydrophobic</scene>, but the ends, which contact water, and much of the interior is <scene name='Globular_Proteins/Porin_polar/1'>polar</scene>. <scene name='Globular_Proteins/Porin_polar_phobic/1'>Both</scene> shown together.
* <scene name='Globular_Proteins/Concan/1'>Concanavalin</scene> - Example of another lectin. Notice that the tertiary structures of the three lectins are different revealing that the structures can be different but yet have the same general function. There are two antiparallel β-sheets with the hydrophobic sides of the sheets facing each other. They are interlocking β-Sheets or have Greek Key Topology, ''i.e.'' after laying down a strand in a sheet, often the peptide chain loops over to the other sheet and lays down a strand in that sheet.
* <scene name='Globular_Proteins/Crystallin/1'>Gamma-Crystallin</scene> - A protein that is a component of the eye lense. This protein is another example of interlocking β-sheet, two of the Greek key bilayers are connected by a looping peptide segment.
* <scene name='Globular_Proteins/Protein_l9/1'>Ribosomal protein L9</scene> - from B. stearothermophillus, a prokayote. The length of the long α-helix is invariant with other prokayotic L9 proteins.
* <scene name='Globular_Proteins/Flavodxin/1'>Flavodoxin</scene> - This type of structure is also called doubly wound parallel β-sheet because of the loops of α-helices on both sides of the sheet. In some cases these doubly wound sheets contain a few antiparallel strands forming a mixed β-sheet. Can you find the three layers of backbone in these doubly wound sheets contain?
* <scene name='Globular_Proteins/Pg_mutase/1'>Phosphoglycerate mutase</scene> - There is one antiparallel strand in the sheet, and the double winding is more extensive.
* <scene name='Globular_Proteins/Rnase/1'>Ribonuclease H</scene> - endoribonuclease from ''E. coli'' that cleaves the RNA strand of a RNA:DNA duplex and produces oligonucleotides. This activity is involved in bacterial replication and required for retrovirial infection. The ''E. coli'' enzyme is homologous with retrovirial proteins.
* <scene name='Globular_Proteins/Ruva/1'>RuvA protein</scene> - ''E. coli'' protein that binds DNA along with RuvB, a helicase, and both are involved in DNA repair, SOS response and DNA recombination. Residues 143-156 are misssing.
* <scene name='Globular_Proteins/Horseshoe/1'>Porcine ribonuclease inhibitor</scene> - contains leucine-rich repeats.

</StructureSection>
<table width='500' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Tertiary Structures of Examples'''<scene name='Globular_Proteins/Two_layers/2'> (Initial scene)</scene></center></td></tr></table>
{{Clear}}
== Other Characteristics ==
Disulfide bonds and metal ion chelates can stabilize the tertiary structure in the absence of well organized layers which generate hydrophobic attractions. Some proteins are small in size and therefore do not have large amounts of backbone that can be organized into layers. Others have significant backbone, but the layers are not well organized and therefore are non-stabilizing. The attractions formed by metal ions chelates or disulfide bonds in these proteins are as important or more so than the hydrophobic interactions of the organized layers. Examples of both types of bonds will be given.

Some proteins or peptide segments are [[Intrinsically_Disordered_Protein |intrinsically disordered]] (unstructured). Whether a complete protein or a protein segment since they are disordered, they can not be crystallized for x-ray crystallographic study. However, when these peptides or peptide segments bind to other proteins they become ordered segments, and can be crystallized along with the binding protein for x-ray crystallographic study. When these peptides bind to other proteins, since their conformations are extended and not compact, the binding occurs over relatively large surface areas of the binding proteins. Examples given below illustrate the extended conformations of the peptide segments as well as the large binding surface. When viewing the unstructured peptides as unbound segments, realize that the conformation which is being displayed is not a disordered conformation but is the conformation of the bound segments with the structure of the binding protein being hidden. If the peptides or peptide fragments were actually free and unbound, since they are unordered, the individual molecules would have a range of conformations and not just one.
<StructureSection load='2ben' size='500' side='right' caption='' scene='Globular_Proteins/Insulin1/1'>__NOTOC__

=== Disulfide-Rich Proteins ===
* <scene name='Globular_Proteins/Insulin1/1'>Insulin</scene> - Among its functions is the regulation of glucose uptake by cells. The small peptide contains A and B chains that are connected by disulfide bonds, and the tertiary structure of the A chain is also held in place by a disulfide bond.
* <scene name='Globular_Proteins/Crambin/1'>Crambin</scene> - Plant seed peptide. Small single chain peptide with no significant backbone layers but has disulfide bonds to stabilize the tertiary structure. Disulfide bonds, also, have an important role of keeping the relatively high proportion of loops in place.
* <scene name='Globular_Proteins/Pholipase2/1'>Phospholipase A2</scene> - Part of a class of hydrolases that degrade glycerophospholipids. This one specifically hydrolyzes the second acyl group on the glycero group. This example is larger than the other two, but it still does not have well organized backbone layers in part due to the extensive turns and loops.

=== Metal-Rich Proteins ===
* <scene name='Globular_Proteins/Hp_iron/1'>High-potential iron protein</scene> - An iron-sulfur protein that has an unusually high redox potential. The Fe's of the iron-sulfur (yellow) center are complexed with the side chains of Cys which are part of different loops of the peptide. Without a large number of hydrophobic groups to form attractions these sulfur-metal bonds are important in maintaining the tertiary structure.
* <scene name='Globular_Proteins/Ferredoxin/1'>Ferredoxin</scene> - Protein with two iron-sulfur centers; the major function of iron-sulfur proteins is involvement in redox reaction. Both iron-sulfur centers are complexed with the side chains of Cys and aid in maintaining the tertiary structure.

=== Intrinsically Unstructured Proteins ===
* <scene name='Globular_Proteins/Lef-1/1'>LEF-1</scene>, lymphoid enhancer-binding factor 1. LEF-1 is missing residues 26-47, and these residues are most likely missing because they form an unordered segment. Fill in this gap in your mind's eye, and you will see the large <scene name='Globular_Proteins/Lef-1_2/1'>surface area</scene> with which LEF-1 (yellow) binds to β-catenin. Apparently the binding strength of the missing segment is such that it is not converted to an ordered segment. You may notice that residues 550-561 of β-catenin are also missing, again an unordered segment.
* <scene name='Globular_Proteins/Snap2/2'>SNAP-25</scene> - Domain N2 of synaptosomal-associated protein 25 (blue) from human bound to botulinum neurotoxin type A light chain (botox) from ''C. botulinum''. <scene name='Globular_Proteins/Snap/2'>Domain N2</scene> shown unbound but having the same conformation as the bound peptide.
* <scene name='Globular_Proteins/Sara_sbd2/1'>SARA SBD</scene> - SMAD Anchor for Receptor Activation SMAD-Binding Domain bound to SMAD2 MH2 domain. SARA SBD is the domain of the receptor that binds SMAD, and thereby activates the transforming growth factor-beta signaling pathway. <scene name='Globular_Proteins/Sara_sbd/2'>SMAD-binding domain</scene> shown unbound and displayed as cartoon but having the same conformation as the bound peptide.
* <scene name='Globular_Proteins/Hif-1alpha2/2'>HIF-1alpha</scene> - Hypoxia-inducing factor 1α (C-terminal activation domain) bound to transcription activation zinc finger domain of CREB-binding protein. <scene name='Globular_Proteins/Hif-1alpha/2'>HIF</scene> shown unbound and displayed as cartoon but having the same conformation as the bound peptide. The data of this model was generated by NMR analysis of an aqueous solution of the peptides, and the analysis is rapid enough to distinguish the vibrations of the peptides so that more than one model is produced. It is possible to animate these multiple model and simulate the vibrations of the peptides. Notice that the vibrations are the greatest in the molecules where the attractive forces are the weakest. Animate peptides: Unbound <scene name='Globular_Proteins/Hif-1alpha/1'>HIF</scene>; Bound <scene name='Globular_Proteins/Hif-1alpha2/1'>HIF</scene>
* <scene name='Globular_Proteins/P27-cdk2/1'>p27-Cdk2-Cyclin A</scene> - Cyclin-dependent kinase 2 bound to its activator cyclin A and both bound with a fragment (blue) of p27 which is a kinase inhibitor. Cyclin-dependent kinases have an important role in moving the cell from one phase of the cell cycle to another. <scene name='Globular_Proteins/P27-cdk2-2/2'>p27</scene> shown unbound but having the same conformation as the bound peptide.
* <scene name='Globular_Proteins/P27_30-35/1'>p27 (30-35)-Cdk2-Cyclin A</scene> - different data file than the one above containing a smaller fragment of p27 bound to complex. <scene name='Globular_Proteins/P27_30-35-2/1'>p27</scene> shown unbound but having the same conformation as the bound peptide. Compare the conformation of this small fragment to that of the yellow colored fragment shown unbound above. Since the binding site is the same in both models when the peptides bind, regardless of the length, the peptides generate the same conformation.
</StructureSection>

==References==
{{Reflist}}

User:Karl Oberholser/Sandbox 1

2012-11-05T21:23:48Z

Karl Oberholser:

<center><H2></H2></center>

<Structure load='PDB=1a7v' size='500' frame='true' align='right' caption='Insert caption here' scene='Globular_Proteins/Two_layers/2' />

== Comparing same scene on two different pages ==
Original scene, Globular_Proteins/Two_layers_phobic/1, with green link 'hydrophobic side chain' was made for [[Globular Proteins]], and chain B is hide with only chain A being displayed. When the same scene <scene name='Globular_Proteins/Two_layers_phobic/1'> hydrophobic side chains</scene> is displayed on this page fragments of chain B in wireframe is displayed in addition to chain A.
== Investigating Contact: ==

<scene name='User:Karl_Oberholser/Sandbox_1/Two_layers_contact/1'>test contact vdw</scene>

==Notes and References==
<references/>

User:Karl Oberholser/Sandbox 1

2012-11-05T21:13:41Z

Karl Oberholser:

<center><H2></H2></center>

{{STRUCTURE_1a7v | PDB=1a7v | SCENE='Globular_Proteins/Two_layers_phobic/1'}}scene ='Globular_Proteins/Two_layers/2'

== Comparing same scene on two different pages ==
Original scene, Globular_Proteins/Two_layers_phobic/1, with green link 'hydrophobic side chain' was made for [[Globular Proteins]], and chain B is hide with only chain A being displayed. When the same scene <scene name='Globular_Proteins/Two_layers_phobic/1'> hydrophobic side chains</scene> is displayed on this page fragments of chain B in wireframe is displayed in addition to chain A.
== Investigating Contact: ==

<scene name='User:Karl_Oberholser/Sandbox_1/Two_layers_contact/1'>test contact vdw</scene>

==Notes and References==
<references/>

User:Karl Oberholser/Sandbox 1

2012-10-29T18:54:32Z

Karl Oberholser:

<center><H2></H2></center>

{{STRUCTURE_1a7v | PDB=1a7v | SCENE='Globular_Proteins/Two_layers_phobic/1'}}

== Comparing same scene on two different pages ==
Original scene with green link 'hydrophobic side chain' is found at [[Globular Proteins]], and only chain A is displayed. When the same scene ('Globular_Proteins/Two_layers_phobic/1')<scene name='Globular_Proteins/Two_layers_phobic/1'> hydrophobic side chains</scene> is displayed on this page fragments of chain B in wireframe is displayed in addition to chain A.
== Investigating Contact: ==

<scene name='User:Karl_Oberholser/Sandbox_1/Two_layers_contact/1'>test contact vdw</scene>

==Notes and References==
<references/>

User:Karl Oberholser/Sandbox 1

2012-10-19T21:04:41Z

Karl Oberholser:

<center><H2></H2></center>

{{STRUCTURE_1a7v | PDB=1a7v | SCENE='Globular_Proteins/Two_layers_phobic/1'}}
<scene name='Globular_Proteins/Two_layers_phobic/1'>test two layers hydrophobic</scene>
== Investigating Contact: ==

<scene name='User:Karl_Oberholser/Sandbox_1/Two_layers_contact/1'>test contact vdw</scene>

==Notes and References==
<references/>

User:Karl Oberholser/Sandbox 1

2012-10-19T20:10:46Z

Karl Oberholser:

<center><H2></H2></center>

{{STRUCTURE_1a7v | PDB=1a7v | SCENE=''}}

== Investigating Contact: ==

<scene name='User:Karl_Oberholser/Sandbox_1/Two_layers_contact/1'>test contact vdw</scene>

{{STRUCTURE_1mbo | PDB=1mbo | SCENE=}}

{{STRUCTURE_2wpy | PDB=2wpy | SCENE=}}
 
 

==Notes and References==
<references/>

Fibroins

2012-10-16T23:56:21Z

Karl Oberholser:

Fibroins are proteins that constitute silk fibers. Fibroins are large complex proteins and the specific structural details of those making up different types of silk are different, but all fibroins have some common characteristics. Interesting general information on spider silk and a model of one type of a spider silk molecule is at<ref>[http://en.wikipedia.org/wiki/Spider_silk Wikipedia]</ref>. This model of spider silk shows two repeating domains that all fibroins contain. One domain is characterized as being amorphous, also called flexible, disordered segments, and the other one, symbolized by the boxes, has a highly ordered, repetitive, crystal-like structure. The objective of this exercise is to explicate this ordered domain of fibroins.

<StructureSection load='fibroin.pdb' size='500' side='right' caption='Structure of a model fibroin' scene='Fibroins/Chain_a/1'>
===Repetitive peptide segment & β-sheet===
Displayed here is a peptide segment that is present in many fibroin proteins that are found in silk fibers. (<scene name='Fibroins/Chain_a/1'>Initial scene</scene>) It is repeated many times to make up the ordered, repetitive structure of the crystalline domain of the fibroin.
 
Determine the sequence of the segment by hovering over the residues taking time to consider the nature of their side chains and from which direction their side chains project from the backbone. All the Gly need to be on the same side of the peptide in order to construct the silk fiber. Labels describe how <scene name='Fibroins/Chain_a_2/1'>hexapeptides are connected</scene> together to produce a longer polypeptide.

A two strand β-sheet is formed by <scene name='Fibroins/Chains_ab/2'>two hexapeptides</scene> positioned antiparallel with respect to each other. Show interchain <scene name='Fibroins/Chains_ab_3/2'>hbonds</scene> which hold chains together. Show <scene name='Fibroins/Chains_ab_3/1'>spacefill</scene> display.

Adding two more chains to form a <scene name='Fibroins/Four_strands/2'>four stranded beta-sheet</scene>. Show <scene name='Fibroins/Four_strands_2/1'>spacefill</scene> rendition.

Two <scene name='Fibroins/Two_sheets/1'>stacked sheets</scene>. The two sheets come together so that the 'Ala side chains' face each other with the methyl and hydroxymethyl groups intercalated. These sheets are attracted to each other and held in place by the hydrophobic forces generated between these side chains. Show interchain <scene name='Fibroins/Two_sheets_2/1'>hbonds</scene> within each sheet. <scene name='Fibroins/Two_sheets_3/1'>Spacefill display</scene> shows that the methyl side chains of the two sheets are close enough to produce hydrophobic forces and that the backbone atoms are close enough to form hbonds.

A <scene name='Fibroins/Three_sheets/1'>third sheet</scene> is stacked with the other two so that the Gly side chains (hydrogen atoms) intercalate. Show <scene name='Fibroins/Three_sheets_2/1'>interchain hbonds</scene> of all three sheets. <scene name='Fibroins/Three_sheets_3/1'>Spacefill rendition</scene> shows that where the Gly side chains come together the backbonds of the sheets are much closer to each other.

Each wireframe chain <scene name='Fibroins/Multicolored/2'>colored differently</scene>. Show <scene name='Fibroins/Multicolored_2/2'>spacefill rendition</scene>.
</StructureSection>

<references />

Collagen

2012-10-13T19:16:21Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a3/8'>Chain C to Pro of Chain A</scene> (green). The force of all these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-10-13T17:05:39Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a3/8'>Chain C to Pro of Chain A</scene> (green). The force of <scene name='Collagen/Hbonds_a_b_c_combined/1'>all these hydrogen bonds</scene> extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-10-12T20:46:08Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a3/2'>Chain C to Pro of Chain A</scene> (green). The force of <scene name='Collagen/Hbonds_a_b_c_combined/1'>all these hydrogen bonds</scene> extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-10-12T17:53:26Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a3/2'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

User:Karl Oberholser

2012-10-12T17:03:59Z

Karl Oberholser:

==Karl Oberholser==
[[Image:Karl 6-08_2.jpg|right|150px]]
Professor Emeritus, Chemistry and Biochemistry Department, Messiah College, Mechanicsburg, PA, USA
 
''<email>oberhols@messiah.edu</email>''
I used HyperChem in my first venture in biomolecular visualization and computation. I eventually made some tutorials in which information was passed between HyperChem and Toolbook. When I became aware of Chime, I focused most of my work on protein structure and function and used Protein Explorer (PE) and Presentations in PE (PiPEs) as they became available. When MolSlides became a feature of PE, I developed an assignment for biochemistry students to make MolSlides of a protein of their choice. In the early years of this work I received a variety of internal grants from Messiah College, and in more recent years I have been receiving release time from teaching. Realizing that Chime was on its death bed I got serious about learning Jmol during the Summer '07 , and during my Fall '07 sabbatical I ported most of the PiPEs to Jmol and converted the last of the HyperChem scripts to Jmol scripts. For most of this work I used α and β versions of Jmol Tutorial-Authoring Template being made by Eric Martz. My first exposure to Proteopedia was mentoring [[User:Emily_Forschler|Emily Forschler]] as she developed [[Photosystem II]].

==Proteopedia Pages==
Introductory Topics
* [[Intro._to_Protein_Structure]]
* [[Carbohydrates]] - Series of pages that focus on aspects of the 3D structure of mono-, di-, and polysaccharides that are not easily illustrated with 2D figures in text books.
* [[Syn_and_anti_nucleosides]] - Illustrates the structural difference between the syn and anti configurations of nucleosides and the steric hindrance that is present in the syn configuration of pyrimidine nucleosides.
Specific proteins
*[[Oxymyoglobin]]
*[[Archaeal_Histones]] - Illustrates the structural features of two histones and the dimer of one of them.
*[[Collagen]] - Illustrates the structure of a collagen segment as well as the structure of a mutated tropocollagen.
*[[Complex III of Electron Transport Chain]] - After illustration of the structures and relative positions of the active peptides, the reactions of the Q cycle are illustrated and explained.
*[[User:Karl_Oberholser/PPDK_large]] - Large frame of a movie of the mechanism of pyruvate phosphate dikinase. The original page with a smaller movie frame and a description of the mechanism is [[Pyruvate_phosphate_dikinase|here]].
*[[User:Karl_Oberholser/Phosphoenolpyruvate:Sugar_Phosphotransferase]] - Large frame of a movie of the mechanism of Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System. The original page with a smaller movie frame and a description of the system and mechanism is [[Enzyme_I_of_the_Phosphoenolpyruvate:Sugar_Phosphotransferase_System|here]].

 

==Other structures and tutorials available in Jmol==
*[http://chemapps.stolaf.edu/klotho Klotho Biochemicals in Jmol] - A searchable list of common biochemicals whose structures can be displayed conveniently in Jmol.
*[http://www.messiah.edu/molscilab/jtat_080120/acetylcholinesterase/contents/contents.htm Acetylcholinesterase]
*[http://biomodel.uah.es/en/model3/index.htm Biomodel-3] - 3D structures of carbohydrates, lipids, amino acids, nucleic acids.
 

== Helpful Pages ==
*[[Help:Editing]]
*[[Help:Color_Keys]]
*[[Help:Copying_FirstGlance_Scenes_into_Proteopedia]]
*[http://proteopedia.org/tools.html Small Molecules]
*[[Proteopedia:Wishlist]]
*[[Proteopedia:Problems]]
*[[What's_new]]
*[[Template:Button_Toggle_Animation]]
*[[Teaching_Strategies_Using_Proteopedia]]
*[http://proteopedia.org/wiki/index.php?limit=100&title=Special%3AContributions&contribs=user&target=Karl+Oberholser&namespace=6&year=&month=-1 Files uploaded by Karl Obeerholser]
*[http://jena3d.fli-leibniz.de/ Jena3D Viewer]
*[[Special:SandboxReservation]]

== Other Useful sites ==
* [http://stolaf.edu/people/hansonr/jmol/contact/ligand.htm Implementation of Jmol '''Contact;''' command]
* [http://proteopedia.org/wiki/index.php/User:Wayne_Decatur/Sandbox_TestCompareinScriptAuthoring Making a fake green link]

Collagen

2012-10-11T21:32:36Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a3/1'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Intro. to Protein Structure

2012-10-10T18:22:17Z

Karl Oberholser:

Articles related to the introduction to protein structure include:
* [[Calculate structure]] - Description of the Jmol command that can be used to highlight helices, sheets and turns of protein structure.
* [[Cation-pi_interactions]]
* [[Coiled_coil]]
* [[Collagen]] - Illustrates the structure of a collagen segment as well as the structure of a mutated tropocollagen.
* [[Fibroins]]
* [[Fibrous Proteins]]
* [[Globular_Proteins]]
* [[Helices in Proteins]]
* [[Intrinsically Disordered Protein]]
* [[Peptide]]
* [[Phi and Psi Angles]]
* [[Ramachandran Plots]]
* [[Secondary structure]]
* [[Sheets in Proteins]]
* [[Structural_templates]]
* [[Thermal_motion_of_peptide]]
* [[Turns in Proteins]]

Psi and Phi Angles

2012-10-10T18:19:51Z

Karl Oberholser: Redirecting to Phi and Psi Angles

#redirect [[Phi and Psi Angles]]

Phi and Psi Angles

2012-10-10T18:16:17Z

Karl Oberholser:

<table width='400' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><applet load='LeuLeuIleTyr.pdb' size='390' frame='true' align='right' scene ='Phi_and_Psi_Angles/First_view/1' caption='' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Tetrapeptide: Leu-Leu-Ile-Tyr'''<scene name='Phi_and_Psi_Angles/First_view/1'> (Initial scene)</scene></center></td></tr></table>

A tetrapeptide, such as Leu-Leu-Ile-Tyr, contains four amino acids connected together with three amide or peptide bonds. Since an amide bond has pi bond character, the six atoms that constitute a peptide bond all lie in the <scene name='Phi_and_Psi_Angles/First__view_planes/1'>same plane</scene> - the orange plane is the peptide bond connecting Tyr and Ile and the yellow one connects Ile and Leu.  As with any peptide the conformation of the <scene name='Phi_and_Psi_Angles/Backbone/1'>backbone</scene> is determined by the values of two torsional angles. In sequence order, phi (φ) is the N(i-1),C(i),Ca(i),N(i) torsion angle and psi (ψ) is the C(i),Ca(i),N(i),C(i+1) torsion angle.

== Determining values for phi (φ) and psi (ψ) ==

The <scene name='Phi_and_Psi_Angles/First_view_phi/1'>four atoms</scene> making up φ are a carbonyl carbon, the connecting α-carbon, an amide nitrogen and the next carbonyl carbon (all marked with green halos). After toggling off spin and rotating the structure so that you can clearly see that you are not clicking on a transparent atom, determine and display the numerical value of φ by double clicking on a carbonyl carbon of the angle, single clicking on the next two atoms and then double clicking on the second carbonly. (If the structure rotates in the course of clicking on the atoms or if you encounter some other problem, re-click on the green link 'four atoms' and restart clicking on the atoms.) The <scene name='Phi_and_Psi_Angles/First__view_psi/1'>four atoms </scene>which constitute a ψ are an amide nitrogen, a carbonyl carbon, an α-carbon and a second nitrogen. After rotating the structure so that the four atoms can be clearly seen, measure and display the numerical value of ψ using the technique described above. <scene name='Phi_and_Psi_Angles/First_draw_rama/1'>Confirm</scene> that you correctly determined direction of rotation and the values of φ and ψ.

<scene name='Phi_and_Psi_Angles/First_view_planes2/1'>Draw the planes</scene> of two other peptide bonds, and then using the technique described above identify the atoms contained in and the numerical values of the φ and ψ angles of the α-carbon connected to these two planes. <scene name='Phi_and_Psi_Angles/Second_draw_rama/1'>Confirm</scene> that you obtained the correct values.

== More Detail on Phi and Psi ==

<table width='400' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><applet load='LeuLeuIleTyr_2models.pdb' size='390' frame='true' align='right' scene ='Phi_and_Psi_Angles/Model_1_ile_angles/1' caption='' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Tetrapeptide: Leu-Leu-Ile-Tyr'''<scene name='Phi_and_Psi_Angles/Model_1_ile_angles/1'> (Initial scene)</scene></center></td></tr></table>

The initial scene shows phi and psi values for Ile. Notice the three colored triangular planes. The yellow plane serves as the references in measuring the two angles. The purple plane is part of the <scene name='Phi_and_Psi_Angles/Model_1_ile_angles_psi_plane/1'>planar peptide bond</scene> (side chains removed for clearer viewing) between Tyr and Ile (red plane), and the angle between the red and yellow planes is psi. The orange plane is part of the <scene name='Phi_and_Psi_Angles/Model_1_ile_angles_phi_plane/1'>planar peptide bond</scene> between Ile and Leu (blue plane), and the angle between the blue and yellow planes is phi. An amino acid needs to be bonded to <scene name='Phi_and_Psi_Angles/Model_1_ile_angles_both_planes/1'>two other amino acids</scene> in order to have values set for both psi and phi, for that reason the two terminal amino acids do not have values set for these angles. Show phi/psi for <scene name='Psi_and_Phi_Angles/Model_1_ile_leu_angles/1'>both Ile and Leu47</scene>. Notice that the orange plane involved in setting phi = -149o is in the same peptide bond plane as the purple plane that sets psi for Leu at -34o. With this being the case the psi for Leu47 can not be set by rotating this peptide bond plane because in doing so the Ile phi value would change. The <scene name='Psi_and_Phi_Angles/Model_1_alpha_c_leu/2'>alpha carbon and its bonded atoms</scene> (larger diameter sticks) can be rotated to set psi for Leu47. Since the <scene name='Psi_and_Phi_Angles/Model_1_carbonyl_c_leu/1'>carbonyl carbon</scene> does not leave the plane of the peptide bond, the rotation of the α-carbon changes the angle of the yellow plane relative to the plane of the peptide bond (orange and purple), and thus sets the the psi for Leu47. The phi for Leu47 is set by rotating the <scene name='Psi_and_Phi_Angles/Model_1_ile_leu_angles_l_l_pla/1'>red plane</scene> (plane of the Leu46-Leu47 peptide bond).

<scene name='Psi_and_Phi_Angles/Model_12_ile_angles/1'>Overlay</scene> with a second peptide (red chain) whose sequence is identical to the original peptide (green chain) and whose phi & psi values are the same except for the Ile which has phi = -49o rather than -149o. The peptides were overlaid so that the Tyr and Ile of the two peptides overlay each other. The peptides diverge at the <scene name='Psi_and_Phi_Angles/Model_12_ile_angles_carbonyl/1'>nitrogens of the Ile's</scene> with the carbonyl groups of Leu47 being in different locations. The yellow reference planes of the two peptides occupy the same space, and therefore since the phi values are different the orange planes are in different locations. Even though the <scene name='Psi_and_Phi_Angles/Both_model_ile_leu_angles/1'>phi and psi of Leu47</scene> are the same in both peptides, the remainder of the peptide chains do not overlay.

=== Displaying Phi and Psi Values ===
The values for these two angles can be determined for the residue of any protein entry in Proteopedia by doing the following:
*In the Jmol applet showing the 3D structure, click on the Jmol logo (or frank) in the bottom right corner.
*When the menu comes up, select '''Console'''.
*Click in the lower text box of the console that comes up, type the '''Select''' command followed by the number of the residue (Obtain this number in the Jmol applet by hovering over the residue whose psi and phi you want to determine), a "''';'''" and the command '''draw rama''' and then press the '''Return''' key.

== External Links ==

[http://en.wikipedia.org/wiki/Torsional_angle Extensive description] of torsional angles.

Phi and Psi Angles

2012-10-10T18:01:21Z

Karl Oberholser:

<table width='400' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><applet load='LeuLeuIleTyr.pdb' size='390' frame='true' align='right' scene ='Phi_and_Psi_Angles/First_view/1' caption='' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Tetrapeptide: Leu-Leu-Ile-Tyr'''<scene name='Phi_and_Psi_Angles/First_view/1'> (Initial scene)</scene></center></td></tr></table>

A tetrapeptide, such as Leu-Leu-Ile-Tyr, contains four amino acids connected together with three amide or peptide bonds. Since an amide bond has pi bond character, the six atoms that constitute a peptide bond all lie in the <scene name='Phi_and_Psi_Angles/First__view_planes/1'>same plane</scene> - the orange plane is the peptide bond connecting Tyr and Ile and the yellow one connects Ile and Leu.  As with any peptide the conformation of the <scene name='Phi_and_Psi_Angles/Backbone/1'>backbone</scene> is determined by the values of two torsional angles. In sequence order, phi (φ) is the N(i-1),C(i),Ca(i),N(i) torsion angle and psi (ψ) is the C(i),Ca(i),N(i),C(i+1) torsion angle.

== Determining values for phi (φ) and psi (ψ) ==

The <scene name='Phi_and_Psi_Angles/First_view_phi/1'>four atoms</scene> making up φ are a carbonyl carbon, the connecting α-carbon, an amide nitrogen and the next carbonyl carbon (all marked with green halos). After toggling off spin and rotating the structure so that you can clearly see that you are not clicking on a transparent atom, determine and display the numerical value of φ by double clicking on a carbonyl carbon of the angle, single clicking on the next two atoms and then double clicking on the second carbonly. (If the structure rotates in the course of clicking on the atoms or if you encounter some other problem, re-click on the green link 'four atoms' and restart clicking on the atoms.) The <scene name='Phi_and_Psi_Angles/First__view_psi/1'>four atoms </scene>which constitute a ψ are an amide nitrogen, a carbonyl carbon, an α-carbon and a second nitrogen. After rotating the structure so that the four atoms can be clearly seen, measure and display the numerical value of ψ using the technique described above. <scene name='Phi_and_Psi_Angles/First_draw_rama/1'>Confirm</scene> that you correctly determined direction of rotation and the values of φ and ψ.

<scene name='Phi_and_Psi_Angles/First_view_planes2/1'>Draw the planes</scene> of two other peptide bonds, and then using the technique described above identify the atoms contained in and the numerical values of the φ and ψ angles of the α-carbon connected to these two planes. <scene name='Phi_and_Psi_Angles/Second_draw_rama/1'>Confirm</scene> that you obtained the correct values.

== More Detail on Phi and Psi ==

<table width='400' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><applet load='LeuLeuIleTyr_2models.pdb' size='390' frame='true' align='right' scene ='Phi_and_Psi_Angles/Model_1_ile_angles/1' caption='' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Tetrapeptide: Leu-Leu-Ile-Tyr'''<scene name='Phi_and_Psi_Angles/Model_1_ile_angles/1'> (Initial scene)</scene></center></td></tr></table>

The initial scene shows phi and psi values for Ile. Notice the three colored triangular planes. The yellow plane serves as the references in measuring the two angles. The purple plane is part of the <scene name='Phi_and_Psi_Angles/Model_1_ile_angles_psi_plane/1'>planar peptide bond</scene> (side chains removed for clearer viewing) between Tyr and Ile (red plane), and the angle between the red and yellow planes is psi. The orange plane is part of the <scene name='Phi_and_Psi_Angles/Model_1_ile_angles_phi_plane/1'>planar peptide bond</scene> between Ile and Leu (blue plane), and the angle between the blue and yellow planes is phi. An amino acid needs to be bonded to <scene name='Phi_and_Psi_Angles/Model_1_ile_angles_both_planes/1'>two other amino acids</scene> in order to have values set for both psi and phi, for that reason the two terminal amino acids do not have values set for these angles. Show phi/psi for <scene name='Psi_and_Phi_Angles/Model_1_ile_leu_angles/1'>both Ile and Leu47</scene>. Notice that the orange plane involved in setting phi = -149o is in the same peptide bond plane as the purple plane that sets psi for Leu at -34o. With this being the case the psi for Leu47 can not be set by rotating this peptide bond plane because in doing so the Ile phi value would change. The <scene name='Psi_and_Phi_Angles/Model_1_alpha_c_leu/2'>alpha carbon and its bonded atoms</scene> (larger diameter sticks) can be rotated to set psi for Leu47. Since the <scene name='Psi_and_Phi_Angles/Model_1_carbonyl_c_leu/1'>carbonyl carbon</scene> does not leave the plane of the peptide bond, the rotation of the α-carbon changes the angle of the yellow plane relative to the plane of the peptide bond (orange and purple), and thus sets the the psi for Leu47. The phi for Leu47 is set by rotating the <scene name='Psi_and_Phi_Angles/Model_1_ile_leu_angles_l_l_pla/1'>red plane</scene> (plane of the Leu46-Leu47 peptide bond).

Show <scene name='Psi_and_Phi_Angles/Model_12_ile_angles/1'>Overlay</scene> with a second peptide (red chain) whose sequence is identical to the original peptide (green chain) and whose phi & psi values are the same except for the Ile which has phi = -49o rather than -149o. The peptides were overlaid so that the Tyr and Ile of the two peptides overlay each other. The peptides diverge at the <scene name='Psi_and_Phi_Angles/Model_12_ile_angles_carbonyl/1'>carbonyl group</scene> of Leu47, the yellow reference planes of the two peptides occupy the same space, and therefore since the phi values are different the orange planes are in different locations. The remainder of the peptide chains do not overlay, even though the <scene name='Psi_and_Phi_Angles/Both_model_ile_leu_angles/1'>psi and phi of Leu47</scene> are the same in both peptides.

=== Displaying Phi and Psi Values ===
The values for these two angles can be determined for the residue of any protein entry in Proteopedia by doing the following:
*In the Jmol applet showing the 3D structure, click on the Jmol logo (or frank) in the bottom right corner.
*When the menu comes up, select '''Console'''.
*Click in the lower text box of the console that comes up, type the '''Select''' command followed by the number of the residue (Obtain this number in the Jmol applet by hovering over the residue whose psi and phi you want to determine), a "''';'''" and the command '''draw rama''' and then press the '''Return''' key.

== External Links ==

[http://en.wikipedia.org/wiki/Torsional_angle Extensive description] of torsional angles.

Interferon

2012-10-09T18:08:54Z

Karl Oberholser:

'''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were classified as interferons because they interfered with virus growth.<ref name="Isaacs" /> The initial experiments performed poorly characterized the interferons, and was based merely on bioactivity. Advances in scientific instrumentation and technique have allowed for greater understanding and visualization of not only the structure but also the mechanisms of the various types of inteferons.<ref name="Structure">PMID:2413490</ref> The interferons were originally classified as leukocyte (interferon-α), fibroblast (interferon-β), and immmune (interferon-γ), although today they are classified into types I (α, β, ε, κ, ω), II (γ), and III (λ).<ref name="Isaacs" /><ref name="Structure" />

{{Clear}}

<StructureSection load='2hym' size='500' side='right' caption='Click on the green links to the left to view the structural aspects of interferons. PDB ID: [[2hym]])' scene='Interferons/Interferonaandreceptor/2'>
==Type I==
Type I interferons are homologous helical cytokines that effect a wide variety of cells pleiotropically. These effects range from antiviral activity to antibacterial, antiprozoal, immunodulatory, and cell growth regulatory functions. Without Type I interferons, the survival of the higher vertebrates would be impossible. Because of their strong antiviral and antiproliferative effects, these interferons are used in the treatment of numerous cancers, hepatitis C, and multiple sclerosis.

All type I interferons bind to a cell surface receptor consisting of two subunits: IFNAR1 and IFNAR2. These receptors belong to a class II helical cytokine receptor family (HCRII). Other members of this family include the interferon-γ receptor (IFNGR), tissue factor (TF), the interleukin 10 receptor (IL20R1 and IL20R2), IL-28BP, IFNLR, and IL28Rα.<ref>PMID:17001036</ref>

===Interferon-α===

Interferon alpha has many <scene name='Multiple_sclerosis/Ifna_labeled/1'>identifiable regions</scene> with two <scene name='Multiple_sclerosis/Ifna_disulfide_bonds/1'>disulfide bonds</scene>: one between the <scene name='Multiple_sclerosis/Ifna_disulfide_bondsn-e/1'>N-terminus and Helix E</scene>, and the other between <scene name='Multiple_sclerosis/Ifna_disulfide_bonds_ab-g/1'>Loop AB and Helix G</scene>. It has seven <scene name='Multiple_sclerosis/Ifna_alphahelices/1'>alpha helices</scene> and has several <scene name='Multiple_sclerosis/Ifna_loops_regions/1'>loop regions.</scene> The helices A, C, and F run <scene name='Multiple_sclerosis/Ifna_parallelacf/2'>parallel</scene> to one another, and <scene name='Multiple_sclerosis/Ifna_antiparallel/1'>anti-parallel</scene> to B, E, and G which run <scene name='Multiple_sclerosis/Ifna_parallel_beg/2'>parallel</scene> to each other.
<scene name='Multiple_sclerosis/Ifna_notparalleltoanyoned/1'>Helix D</scene> does not run parallel or anti-parallel to either set, but rather runs at a 45-90 degree angle to them. Helix A consists of residues 10-12; Helix B of 40-43; Helix C of 53-68; Helix D of 70-75; Helix E of 78-100; Helix F of 109-132; and Helix G of 137-158.

===Interferon-β===
A protein growth factor that stimulates an antiviral defense <scene name='Multiple_sclerosis/Interferon_beta/9'>interferon-beta</scene> is one of the only two known vertebrate structural genes that lacks introns.<ref name="Biochem Text">Voet, D., Voet, J.G., and C. Pratt. ''Fundamentals of Biochemistry'' 3rd Edition. Hoboken, NJ: John Wiley and Sons, 2008. Print.</ref> Interferon-β has a 31% sequence homology to interferon-α . It is a relatively simple biological response modifier, with several <scene name='Multiple_sclerosis/Interferon_beta_labeled/1'>identifiable regions</scene>. It consists of five <scene name='Multiple_sclerosis/Ifnb_helices_in_color/1'>alpha helices</scene>, as compared to the seven of interferon-α, as well as multiple interconnecting <scene name='Multiple_sclerosis/Interferon_beta_loops/2'>loop regions</scene>. Helices A, B and D run <scene name='Multiple_sclerosis/Ifnb_parallel_abd/3'>parallel to one another</scene>, and helices C and E run <scene name='Multiple_sclerosis/Ifnb_antiparallel/1'>anti-parallel</scene> to the other three helices, but <scene name='Multiple_sclerosis/Ifnb_antiparallel_ce/3'>parallel</scene> to one another. Helix A consists of residues 6-23; Helix B consists of residues 49-65; Helix C consists of residues 77-91; Helix D consists of residues 112-131; and Helix E consists of residues 135-155.<ref name="Structure Ifn B">PMID:20616576</ref><ref name="UniProt">http://www.uniprot.org/uniprot/P00784</ref>

Interferon-β is used as a treatment for [[Multiple sclerosis]], an autoimmune disease defined by Nylander and Hafler as "a multifocal demyelinating disease with progressive neurodegeneration caused by an autoimmune response to self-antigens in a genetically susceptible individual."<ref name ="MS Nylander & Hafler">PMID:22466660</ref> Inflammation is the primary cause of damage in MS, and though the effects of the disease are well known and various treatments exist for the disease, the exact identity of an antigen or infectious agent that causes the initiation of a myriad of symptoms is unknown.<ref name='MS:Pathogenesis and Treatment'>PMID:22379455</ref>

__NOTOC__
</StructureSection>

== Comparison of three interferons ==
{|
|<applet load='1ITF.pdb' name='A' size='300' frame='true' align='right' caption='Interferon Alpha' align='left' scene='Interferon/Ifn_alpha/5'/>
|<applet load='1IFA.pdb' name='B' size='300' frame='true' align='right' caption='Interferon Beta' align='left' scene='Interferon/Interferon_beta/4'/>
|<applet load='1HIG.pdb' name='Z' size='300' frame='true' align='right' caption='Interferon Gamma' align='left' scene='Interferon/Ifn_gamma/5'/>
|}
<center>

'''Synchronize the three applets showing interferons alpha, beta, and gamma by clicking the checkbox'''
<jmol>
<jmolCheckbox>
<target>A</target>

<scriptWhenChecked> sync jmolAppletB,jmolAppletZ </scriptWhenChecked>
<scriptWhenUnchecked> sync OFF</scriptWhenUnchecked>
<text> Synchronize</text>
</jmolCheckbox>
</jmol>
</center>

[[Image:InterferonSignalingPathway.png|600px|right|thumb|Interferon JAK-STAT Pathway showing interferons types I, II, and III<ref name="Isaacs">[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref>]]

==Signaling and Receptor Interactions==

The signaling pathways of interferons are interesting as type I interferons share the same receptors IFNAR1 and IFNAR2. Type II interferon-γ has receptors IFNGR1 and IFNGR2, but needs two interferon-γ to signal, as illustrated in the image to the right. Interestingly enough, types I and III act together in the JAK-STAT pathway, while type II acts alone. Interferon-α and -β bind to the same receptors as one another, the affinities with which they bind to IFNAR1 and IFNAR2 differ. While the binding to IFNAR2 is stronger for both in comparison to IFNAR1, interferon-β has a much stronger affinity for IFNAR1 than interferon-α.<ref name="Interferon Receptor Interferon Alpha">PMID:17001036</ref>

Interferon-α <scene name='Multiple_sclerosis/Ifnawithreceptorcolored/1'>binds</scene> to an interferon receptor mainly with helices C and G. There are many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/2'>residues</scene> within 4 angstroms of one another. These residues could form many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/5'>different types of bonds</scene>, illustrated in white dotted lines. Given that interferon-α does not undergo many structural changes upon binding to interferon receptor II, Quadt-Akabayov et al. have concluded that the binding mechanism is similar to that of a lock and key. Interferons -α and -β interact with a receptor at the cell surface.<ref>[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref> This receptor has <scene name='Multiple_sclerosis/Ifnr_domains_labeled/1'>three domains</scene>: an
<scene name='Multiple_sclerosis/Ifnr_n_domain_labeled/1'>N-domain</scene>, with two disulfide bonds, a <scene name='Multiple_sclerosis/Ifnr_c_domain_labeled/1'>C-domain</scene>, with one disulfide bond, and a <scene name='Multiple_sclerosis/Ifnr_linker_region_labeled/1'>linker region</scene>. The <scene name='Multiple_sclerosis/Ifnr_termini_labeled/1'>termini regions</scene> of the receptor have no secondary structure, allowing for some serious flexibility, leading to <scene name='Multiple_sclerosis/Ifnr_clash_n-c/1'>eight clashes amongst the domains</scene>.<ref name="Interferon Receptor Structure">PMID:12842042</ref>

==References==

<references />

==3D Structures of interferon==

===Interferon-α===

[[1itf]] - hIF 2A – NMR 
[[2hym]], [[2kz1]], [[2lag]], [[3s9d]] - hIF 2A + IFR α/β 
[[2rh2]] – hIF 2B 
[[3se3]] - hIF 2B + IFR 1 + IFR 2 
[[3oq3]] - hIF 5 + IFR α/β

===Interferon-β===

[[1ifa]], [[1wu3]] – IF – mouse 
[[1au1]] - hIF

===Interferon-γ===

[[1hig]] – hIF – human 
[[1eku]] – hIF (mutant) 
[[2rig]] – IF – rabbit 
[[1rfb]], [[1d9c]] – IF – bovine 
[[1fg9]], [[1fyh]], [[3bes]] – hIF + IFR α chain

===Interferon-λ===

[[3og4]], [[3og6]] – hIF 1 + IFR 
[[3hhc]] – hIF 4

===Interferon-τ===

[[1b5l]] – IF

===Interferon-ω===

[[3se4]] - hIF 1 + IFR 1 + IFR 2

[[3piv]] – ZfIF 1 – Zebra fish 
[[3piw]] - ZfIF 2

__NOTOC__
[[Category:Topic Page]]

Interferon

2012-10-09T17:54:23Z

Karl Oberholser:

'''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were classified as interferons because they interfered with virus growth.<ref name="Isaacs" /> The initial experiments performed poorly characterized the interferons, and was based merely on bioactivity. Advances in scientific instrumentation and technique have allowed for greater understanding and visualization of not only the structure but also the mechanisms of the various types of inteferons.<ref name="Structure">PMID:2413490</ref> The interferons were originally classified as leukocyte (interferon-α), fibroblast (interferon-β), and immmune (interferon-γ), although today they are classified into types I (α, β, ε, κ, ω), II (γ), and III (λ).<ref name="Isaacs" /><ref name="Structure" />

{{Clear}}

<StructureSection load='2hym' size='500' side='right' caption='Click on the green links to the left to view the structural aspects of interferons. PDB ID: [[2hym]])' scene='Interferons/Interferonaandreceptor/2'>
==Type I==
Type I interferons are homologous helical cytokines that effect a wide variety of cells pleiotropically. These effects range from antiviral activity to antibacterial, antiprozoal, immunodulatory, and cell growth regulatory functions. Without Type I interferons, the survival of the higher vertebrates would be impossible. Because of their strong antiviral and antiproliferative effects, these interferons are used in the treatment of numerous cancers, hepatitis C, and multiple sclerosis.

All type I interferons bind to a cell surface receptor consisting of two subunits: IFNAR1 and IFNAR2. These receptors belong to a class II helical cytokine receptor family (HCRII). Other members of this family include the interferon-γ receptor (IFNGR), tissue factor (TF), the interleukin 10 receptor (IL20R1 and IL20R2), IL-28BP, IFNLR, and IL28Rα.<ref>PMID:17001036</ref>

===Interferon-α===

Interferon alpha has many <scene name='Multiple_sclerosis/Ifna_labeled/1'>identifiable regions</scene> with two <scene name='Multiple_sclerosis/Ifna_disulfide_bonds/1'>disulfide bonds</scene>: one between the <scene name='Multiple_sclerosis/Ifna_disulfide_bondsn-e/1'>N-terminus and Helix E</scene>, and the other between <scene name='Multiple_sclerosis/Ifna_disulfide_bonds_ab-g/1'>Loop AB and Helix G</scene>. It has seven <scene name='Multiple_sclerosis/Ifna_alphahelices/1'>alpha helices</scene> and has several <scene name='Multiple_sclerosis/Ifna_loops_regions/1'>loop regions.</scene> The helices A, C, and F run <scene name='Multiple_sclerosis/Ifna_parallelacf/2'>parallel</scene> to one another, and <scene name='Multiple_sclerosis/Ifna_antiparallel/1'>anti-parallel</scene> to B, E, and G which run <scene name='Multiple_sclerosis/Ifna_parallel_beg/2'>parallel</scene> to each other.
<scene name='Multiple_sclerosis/Ifna_notparalleltoanyoned/1'>Helix D</scene> does not run parallel or anti-parallel to either set, but rather runs at a 45-90 degree angle to them. Helix A consists of residues 10-12; Helix B of 40-43; Helix C of 53-68; Helix D of 70-75; Helix E of 78-100; Helix F of 109-132; and Helix G of 137-158.

===Interferon-β===
A protein growth factor that stimulates an antiviral defense <scene name='Multiple_sclerosis/Interferon_beta/9'>interferon-beta</scene> is one of the only two known vertebrate structural genes that lacks introns.<ref name="Biochem Text">Voet, D., Voet, J.G., and C. Pratt. ''Fundamentals of Biochemistry'' 3rd Edition. Hoboken, NJ: John Wiley and Sons, 2008. Print.</ref> Interferon-β has a 31% sequence homology to interferon-α . It is a relatively simple biological response modifier, with several <scene name='Multiple_sclerosis/Interferon_beta_labeled/1'>identifiable regions</scene>. It consists of five <scene name='Multiple_sclerosis/Ifnb_helices_in_color/1'>alpha helices</scene>, as compared to the seven of interferon-α, as well as multiple interconnecting <scene name='Multiple_sclerosis/Interferon_beta_loops/2'>loop regions</scene>. Helices A, B and D run <scene name='Multiple_sclerosis/Ifnb_parallel_abd/3'>parallel to one another</scene>, and helices C and E run <scene name='Multiple_sclerosis/Ifnb_antiparallel/1'>anti-parallel</scene> to the other three helices, but <scene name='Multiple_sclerosis/Ifnb_antiparallel_ce/3'>parallel</scene> to one another. Helix A consists of residues 6-23; Helix B consists of residues 49-65; Helix C consists of residues 77-91; Helix D consists of residues 112-131; and Helix E consists of residues 135-155.<ref name="Structure Ifn B">PMID:20616576</ref><ref name="UniProt">http://www.uniprot.org/uniprot/P00784</ref>

Interferon-β is used as a treatment for [[Multiple sclerosis]], an autoimmune disease defined by Nylander and Hafler as "a multifocal demyelinating disease with progressive neurodegeneration caused by an autoimmune response to self-antigens in a genetically susceptible individual."<ref name ="MS Nylander & Hafler">PMID:22466660</ref> Inflammation is the primary cause of damage in MS, and though the effects of the disease are well known and various treatments exist for the disease, the exact identity of an antigen or infectious agent that causes the initiation of a myriad of symptoms is unknown.<ref name='MS:Pathogenesis and Treatment'>PMID:22379455</ref>

__NOTOC__
</StructureSection>

== Comparison of three interferons ==
{|
|<applet load='1ITF.pdb' name='A' size='300' frame='true' align='right' caption='Interferon Alpha' align='left' scene='Interferon/Ifn_alpha/5'/>
|<applet load='1IFA.pdb' name='B' size='300' frame='true' align='right' caption='Interferon Beta' align='left' scene='Interferon/Interferon_beta/4'/>
|<applet load='1HIG.pdb' name='Z' size='300' frame='true' align='right' caption='Interferon Gamma' align='left' scene='Interferon/Ifn_gamma/5'/>
|}
[[Image:InterferonSignalingPathway.png|600px|right|thumb|Interferon JAK-STAT Pathway showing interferons types I, II, and III<ref name="Isaacs">[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref>]]

==Signaling and Receptor Interactions==

The signaling pathways of interferons are interesting as type I interferons share the same receptors IFNAR1 and IFNAR2. Type II interferon-γ has receptors IFNGR1 and IFNGR2, but needs two interferon-γ to signal, as illustrated in the image to the right. Interestingly enough, types I and III act together in the JAK-STAT pathway, while type II acts alone. Interferon-α and -β bind to the same receptors as one another, the affinities with which they bind to IFNAR1 and IFNAR2 differ. While the binding to IFNAR2 is stronger for both in comparison to IFNAR1, interferon-β has a much stronger affinity for IFNAR1 than interferon-α.<ref name="Interferon Receptor Interferon Alpha">PMID:17001036</ref>

Interferon-α <scene name='Multiple_sclerosis/Ifnawithreceptorcolored/1'>binds</scene> to an interferon receptor mainly with helices C and G. There are many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/2'>residues</scene> within 4 angstroms of one another. These residues could form many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/5'>different types of bonds</scene>, illustrated in white dotted lines. Given that interferon-α does not undergo many structural changes upon binding to interferon receptor II, Quadt-Akabayov et al. have concluded that the binding mechanism is similar to that of a lock and key. Interferons -α and -β interact with a receptor at the cell surface.<ref>[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref> This receptor has <scene name='Multiple_sclerosis/Ifnr_domains_labeled/1'>three domains</scene>: an
<scene name='Multiple_sclerosis/Ifnr_n_domain_labeled/1'>N-domain</scene>, with two disulfide bonds, a <scene name='Multiple_sclerosis/Ifnr_c_domain_labeled/1'>C-domain</scene>, with one disulfide bond, and a <scene name='Multiple_sclerosis/Ifnr_linker_region_labeled/1'>linker region</scene>. The <scene name='Multiple_sclerosis/Ifnr_termini_labeled/1'>termini regions</scene> of the receptor have no secondary structure, allowing for some serious flexibility, leading to <scene name='Multiple_sclerosis/Ifnr_clash_n-c/1'>eight clashes amongst the domains</scene>.<ref name="Interferon Receptor Structure">PMID:12842042</ref>

==References==

<references />

==3D Structures of interferon==

===Interferon-α===

[[1itf]] - hIF 2A – NMR 
[[2hym]], [[2kz1]], [[2lag]], [[3s9d]] - hIF 2A + IFR α/β 
[[2rh2]] – hIF 2B 
[[3se3]] - hIF 2B + IFR 1 + IFR 2 
[[3oq3]] - hIF 5 + IFR α/β

===Interferon-β===

[[1ifa]], [[1wu3]] – IF – mouse 
[[1au1]] - hIF

===Interferon-γ===

[[1hig]] – hIF – human 
[[1eku]] – hIF (mutant) 
[[2rig]] – IF – rabbit 
[[1rfb]], [[1d9c]] – IF – bovine 
[[1fg9]], [[1fyh]], [[3bes]] – hIF + IFR α chain

===Interferon-λ===

[[3og4]], [[3og6]] – hIF 1 + IFR 
[[3hhc]] – hIF 4

===Interferon-τ===

[[1b5l]] – IF

===Interferon-ω===

[[3se4]] - hIF 1 + IFR 1 + IFR 2

[[3piv]] – ZfIF 1 – Zebra fish 
[[3piw]] - ZfIF 2

__NOTOC__
[[Category:Topic Page]]

Interferon

2012-10-09T17:43:28Z

Karl Oberholser:

'''Interferons''' were the first cytokines discovered and were identified by Isaacs and Lindenmann. These proteins were classified as interferons because they interfered with virus growth.<ref name="Isaacs" /> The initial experiments performed poorly characterized the interferons, and was based merely on bioactivity. Advances in scientific instrumentation and technique have allowed for greater understanding and visualization of not only the structure but also the mechanisms of the various types of inteferons.<ref name="Structure">PMID:2413490</ref> The interferons were originally classified as leukocyte (interferon-α), fibroblast (interferon-β), and immmune (interferon-γ), although today they are classified into types I (α, β, ε, κ, ω), II (γ), and III (λ).<ref name="Isaacs" /><ref name="Structure" />

{{Clear}}

<StructureSection load='2hym' size='500' side='right' caption='Click on the green links to the left to view the structural aspects of interferons. PDB ID: [[2hym]])' scene='Interferons/Interferonaandreceptor/2'>
==Type I==
Type I interferons are homologous helical cytokines that effect a wide variety of cells pleiotropically. These effects range from antiviral activity to antibacterial, antiprozoal, immunodulatory, and cell growth regulatory functions. Without Type I interferons, the survival of the higher vertebrates would be impossible. Because of their strong antiviral and antiproliferative effects, these interferons are used in the treatment of numerous cancers, hepatitis C, and multiple sclerosis.

All type I interferons bind to a cell surface receptor consisting of two subunits: IFNAR1 and IFNAR2. These receptors belong to a class II helical cytokine receptor family (HCRII). Other members of this family include the interferon-γ receptor (IFNGR), tissue factor (TF), the interleukin 10 receptor (IL20R1 and IL20R2), IL-28BP, IFNLR, and IL28Rα.<ref>PMID:17001036</ref>

===Interferon-α===

Interferon alpha has many <scene name='Multiple_sclerosis/Ifna_labeled/1'>identifiable regions</scene> with two <scene name='Multiple_sclerosis/Ifna_disulfide_bonds/1'>disulfide bonds</scene>: one between the <scene name='Multiple_sclerosis/Ifna_disulfide_bondsn-e/1'>N-terminus and Helix E</scene>, and the other between <scene name='Multiple_sclerosis/Ifna_disulfide_bonds_ab-g/1'>Loop AB and Helix G</scene>. It has seven <scene name='Multiple_sclerosis/Ifna_alphahelices/1'>alpha helices</scene> and has several <scene name='Multiple_sclerosis/Ifna_loops_regions/1'>loop regions.</scene> The helices A, C, and F run <scene name='Multiple_sclerosis/Ifna_parallelacf/2'>parallel</scene> to one another, and <scene name='Multiple_sclerosis/Ifna_antiparallel/1'>anti-parallel</scene> to B, E, and G which run <scene name='Multiple_sclerosis/Ifna_parallel_beg/2'>parallel</scene> to each other.
<scene name='Multiple_sclerosis/Ifna_notparalleltoanyoned/1'>Helix D</scene> does not run parallel or anti-parallel to either set, but rather runs at a 45-90 degree angle to them. Helix A consists of residues 10-12; Helix B of 40-43; Helix C of 53-68; Helix D of 70-75; Helix E of 78-100; Helix F of 109-132; and Helix G of 137-158.

===Interferon-β===
A protein growth factor that stimulates an antiviral defense <scene name='Multiple_sclerosis/Interferon_beta/9'>interferon-beta</scene> is one of the only two known vertebrate structural genes that lacks introns.<ref name="Biochem Text">Voet, D., Voet, J.G., and C. Pratt. ''Fundamentals of Biochemistry'' 3rd Edition. Hoboken, NJ: John Wiley and Sons, 2008. Print.</ref> Interferon-β has a 31% sequence homology to interferon-α . It is a relatively simple biological response modifier, with several <scene name='Multiple_sclerosis/Interferon_beta_labeled/1'>identifiable regions</scene>. It consists of five <scene name='Multiple_sclerosis/Ifnb_helices_in_color/1'>alpha helices</scene>, as compared to the seven of interferon-α, as well as multiple interconnecting <scene name='Multiple_sclerosis/Interferon_beta_loops/2'>loop regions</scene>. Helices A, B and D run <scene name='Multiple_sclerosis/Ifnb_parallel_abd/3'>parallel to one another</scene>, and helices C and E run <scene name='Multiple_sclerosis/Ifnb_antiparallel/1'>anti-parallel</scene> to the other three helices, but <scene name='Multiple_sclerosis/Ifnb_antiparallel_ce/3'>parallel</scene> to one another. Helix A consists of residues 6-23; Helix B consists of residues 49-65; Helix C consists of residues 77-91; Helix D consists of residues 112-131; and Helix E consists of residues 135-155.<ref name="Structure Ifn B">PMID:20616576</ref><ref name="UniProt">http://www.uniprot.org/uniprot/P00784</ref>

Interferon-β is used as a treatment for [[Multiple sclerosis]], an autoimmune disease defined by Nylander and Hafler as "a multifocal demyelinating disease with progressive neurodegeneration caused by an autoimmune response to self-antigens in a genetically susceptible individual."<ref name ="MS Nylander & Hafler">PMID:22466660</ref> Inflammation is the primary cause of damage in MS, and though the effects of the disease are well known and various treatments exist for the disease, the exact identity of an antigen or infectious agent that causes the initiation of a myriad of symptoms is unknown.<ref name='MS:Pathogenesis and Treatment'>PMID:22379455</ref>

__NOTOC__
</StructureSection>

== Comparison of three interferons ==
{|
|<applet load='1ITF.pdb' name='A' size='300' frame='true' align='right' caption='Interferon Alpha' align='left' scene='Interferon/Ifn_alpha/5'/>
|<applet load='1IFA.pdb' name='B' size='300' frame='true' align='right' caption='Interferon Beta' align='left' scene='Sandbox_60/Interferon_beta/1'/>
|<applet load='1HIG.pdb' name='Z' size='300' frame='true' align='right' caption='Interferon Gamma' align='left' scene='Sandbox_60/Ifn_gamma/1'/>
|}
[[Image:InterferonSignalingPathway.png|600px|right|thumb|Interferon JAK-STAT Pathway showing interferons types I, II, and III<ref name="Isaacs">[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref>]]

==Signaling and Receptor Interactions==

The signaling pathways of interferons are interesting as type I interferons share the same receptors IFNAR1 and IFNAR2. Type II interferon-γ has receptors IFNGR1 and IFNGR2, but needs two interferon-γ to signal, as illustrated in the image to the right. Interestingly enough, types I and III act together in the JAK-STAT pathway, while type II acts alone. Interferon-α and -β bind to the same receptors as one another, the affinities with which they bind to IFNAR1 and IFNAR2 differ. While the binding to IFNAR2 is stronger for both in comparison to IFNAR1, interferon-β has a much stronger affinity for IFNAR1 than interferon-α.<ref name="Interferon Receptor Interferon Alpha">PMID:17001036</ref>

Interferon-α <scene name='Multiple_sclerosis/Ifnawithreceptorcolored/1'>binds</scene> to an interferon receptor mainly with helices C and G. There are many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/2'>residues</scene> within 4 angstroms of one another. These residues could form many <scene name='Multiple_sclerosis/Ifnawithreceptorintrxns/5'>different types of bonds</scene>, illustrated in white dotted lines. Given that interferon-α does not undergo many structural changes upon binding to interferon receptor II, Quadt-Akabayov et al. have concluded that the binding mechanism is similar to that of a lock and key. Interferons -α and -β interact with a receptor at the cell surface.<ref>[http://www.jbc.org/content/282/28/20045.full?sid=cbf08059-44d4-4957-8ea7-0351cab9c2ac] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." ''J Biol Chem'' 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200</ref> This receptor has <scene name='Multiple_sclerosis/Ifnr_domains_labeled/1'>three domains</scene>: an
<scene name='Multiple_sclerosis/Ifnr_n_domain_labeled/1'>N-domain</scene>, with two disulfide bonds, a <scene name='Multiple_sclerosis/Ifnr_c_domain_labeled/1'>C-domain</scene>, with one disulfide bond, and a <scene name='Multiple_sclerosis/Ifnr_linker_region_labeled/1'>linker region</scene>. The <scene name='Multiple_sclerosis/Ifnr_termini_labeled/1'>termini regions</scene> of the receptor have no secondary structure, allowing for some serious flexibility, leading to <scene name='Multiple_sclerosis/Ifnr_clash_n-c/1'>eight clashes amongst the domains</scene>.<ref name="Interferon Receptor Structure">PMID:12842042</ref>

==References==

<references />

==3D Structures of interferon==

===Interferon-α===

[[1itf]] - hIF 2A – NMR 
[[2hym]], [[2kz1]], [[2lag]], [[3s9d]] - hIF 2A + IFR α/β 
[[2rh2]] – hIF 2B 
[[3se3]] - hIF 2B + IFR 1 + IFR 2 
[[3oq3]] - hIF 5 + IFR α/β

===Interferon-β===

[[1ifa]], [[1wu3]] – IF – mouse 
[[1au1]] - hIF

===Interferon-γ===

[[1hig]] – hIF – human 
[[1eku]] – hIF (mutant) 
[[2rig]] – IF – rabbit 
[[1rfb]], [[1d9c]] – IF – bovine 
[[1fg9]], [[1fyh]], [[3bes]] – hIF + IFR α chain

===Interferon-λ===

[[3og4]], [[3og6]] – hIF 1 + IFR 
[[3hhc]] – hIF 4

===Interferon-τ===

[[1b5l]] – IF

===Interferon-ω===

[[3se4]] - hIF 1 + IFR 1 + IFR 2

[[3piv]] – ZfIF 1 – Zebra fish 
[[3piw]] - ZfIF 2

__NOTOC__
[[Category:Topic Page]]

Collagen

2012-10-08T23:18:52Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a/1'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-10-08T23:17:10Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a/1'>Chain C to Pro of Chain A</scene> (limegreen). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-10-05T20:45:51Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a/1'>Chain C to Pro of Chain A</scene> (limegreen). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-10-05T15:47:31Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/4'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/3'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Intra-hbonds5/2'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-09-16T18:45:49Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/1'>Show side chains</scene>(<scene name='Collagen/One_peptide_bs/1'>ball and stick</scene>) of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/1'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Intra-hbonds5/2'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-08-15T17:04:56Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/1'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/1'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Intra-hbonds5/2'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Turns in Proteins

2012-08-14T16:10:23Z

Karl Oberholser:

<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/Hemery/4' />__NOTOC__
Turns are classified as a type of secondary structure, but unlike helices and sheets which have ordered, repetitive structures, turns only have ordered structures, but like helices and sheets they can be classified by the values of the torsional angles of the Cα's. This article describes β-turns and γ-turns and illustrates their ordered structures.

== Beta Turns ==
All β-turns contain four residues and are divided into classes based on the range of their [[Psi and Phi Angles|phi and psi]] values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> Most classes have a hydrogen bond between the backbond atoms of residues one(''i'') and four (''i + 3''), and this attraction is the major force maintaining the conformation of the bend in the chain, but in several classes a Pro in the third position (''i + 2'') has the cis configuration which produces a conformation which can not form a hydrogen bond (hbonds).

Seven β-turns are shown as blue traces in myohemerytherin in the scene to the right (<scene name='Turns_in_Proteins/Hemery1/1'>Initial scene</scene>). There are only five blue segments because, in two cases, one β-turn follows another one. Only five of the turns contain hydrogen bonds shown in magenta. As explained in [[Calculate structure]], the '''calculate structure''' command does not detect beta turns which have a Pro in the cis configuration and lack a hbond. Since the command has this limitation, the initial scene was produced by manually selecting and coloring the turns and forming the hbonds. <scene name='Turns_in_Proteins/Calculate_structure/2'>Show</scene> the results of the '''calculate structure''' command.

<blockquote>For reasons explained in the Introduction of [[Calculate structure]], the command to form hbonds of secondary structures was not included in the construction of the above scene, but they can be displayed in any scene by doing the following: click on the Jmol frank, in the main menu click on Console, in the bottom box of the console enter the command: calculate hbonds structure and then click Run.
</blockquote>
<blockquote>Also, if any Proteopedia scene shows the secondary structure and it does not show the beta turns highlighted in blue, the beta turns can be shown in blue by following the above procedure but enter select protein; calculate structure; cartoon; color structure into the bottom box of the console.
</blockquote>

Shown in <scene name='Turns_in_Proteins/Hemery_wf/5'>wireframe</scene> so that one can see the hydrogen bonds are positioned between the first and the fourth residues of the turn and involve backbone atoms. Can you locate the cis configured Pro in the two turns without hbonds? <scene name='Turns_in_Proteins/Rama_2mhr/1'>Ramachandran plot</scene> ([[Ramachandran Plot]]).

{{Clear}}

=== Examples ===
Examples of four of the nine classes<ref name=beta/> of β-turns are shown below with two examples of each of the four classes. The turns were cut from either myohemerytherin (2mhr.pdb) or domain 2 of glycogen phosphorylase chain A (1abb.pdb). Compare the shapes of the turns and observe the differences in the phi (φ) and psi (ψ) values of the second and third residues. Checking the synchronize box will permit you to rotate all the turns by rotating any one of the turns with the mouse.


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 1,2,3,4,5,6,7,8 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 8 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<table style="width:100%;">
<tr align="center">
<th style="width:25%;">Class I
</th>
<th style="width:25%;">Class II
</th>
<th style="width:25%;">Class III
</th>
<th style="width:25%;">Class IV B
</th>
</tr>
<tr align="center">
<td>
<applet load='2mhr 12-15.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_12-15/4' />
</td>

<td>
<applet load='2mhr 114-117.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_114-117/3'/>
</td>
<td>
<applet load='1abb 636-639.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_636-639/1' />
</td>
<td>
<applet load='2mhr 5-8.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_5-8/3'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -66°, ψ = -19°
    Residue 3: φ = -91°, ψ = -1°
</td>
<td>
   Residue 2: φ = -56°, ψ = +126°
    Residue 3: φ = +78°, ψ = +1°
</td>
<td>
   Residue 2: φ = +56°, ψ = -117°
    Residue 3: φ = -125°, ψ = +19°
</td>
<td>
   Residue 2: φ = -135°, ψ = +112°
    Residue 3: φ = -63°, ψ = +163°
</td>
</tr>

<tr align="center">
<td>
<applet load='2mhr 67-70' size='200' frame='false' scene='Turns_in_Proteins/2mhr_67-70/4' />
</td>
<td>
<applet load='1abb 610-613.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_610-613/3' />
</td>
<td>
<applet load='1abb 693-696.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_693-696/2' />
</td>
<td>
<applet load='2mhr 88-91' size='200' frame='false' scene='Turns_in_Proteins/2mhr_88-91/2'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -70°, ψ = -25°
    Residue 3: φ = -109°, ψ = +29°
</td>
<td>
   Residue 2: φ = -53°, ψ = +131°
    Residue 3: φ = +78°, ψ = -10°
</td>
<td>
   Residue 2: φ = +47°, ψ = -122°
    Residue 3: φ = -94°, ψ = +2°
</td>
<td>
   Residue 2: φ = -89°, ψ = +142°
    Residue 3: φ = -76°, ψ = +135°
</td>
</tr>
</table>
<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/2mhr_5-8c/2' />
Turn 2mhr 5-8, classIVB, is shown in the applet on the right. Notice that it does not have a hydrogen bond and that the backbone atoms of the first and fourth residues are not in position to form a hydrogen bond because the presence of a cis peptide bond. (<scene name='Turns_in_Proteins/2mhr_5-8c/2'>Initial scene</scene>) <scene name='Turns_in_Proteins/2mhr_114-117b/2'>Compare</scene> with a turn which has a hbond. The oxygen and nitrogen of the <scene name='Turns_in_Proteins/2mhr_88-91b/2' >cis peptide bond</scene> project from the same edge of the plane, whereas with the trans peptide bonds they project from opposite edges of the plane. The <scene name='Turns_in_Proteins/Rama_8_turns/6'>Ramachandran plot</scene> of the eight turns shown above. Two residues of each turn are plotted giving a total of 16 points. Hover the cursor over a sphere to identify the residue name and number. Realize that, in most cases, the spheres that are of the same class and are close to each other are not part of the same turn. Notice that Gly is the only residue in a [[Ramachandran Plot#Plot regions limited by steric hindrance|disallowed region]] since other residues at those positions could not generate the angles necessary to form the turn and that Pro is the third residue in both class IVB turns.
== Gamma Turns ==
Gamma turns consist of three residues and contain a hydrogen bond between residues one and three. In a search of 54 proteins nine proteins were found to have eleven classic γ-turns, and these eleven turns had mean phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref> Seven of these eleven turns are involved in the formation of β-hairpins which produce a reversal in the peptide chain. Several examples of β-hairpins follow:
* <scene name='Turns_in_Proteins/2alp_classic/3'>Alpha-Lytic protease</scene>; <scene name='Turns_in_Proteins/2alp_classic2/2'>Isolated turn</scene>
* <scene name='Turns_in_Proteins/Proteinase_a/4'>Proteinase A</scene>; <scene name='Turns_in_Proteins/Proteinase_a2/3'>Isolate Turn</scene>
* <scene name='Turns_in_Proteins/Thermolysin/2'>Thermolysin</scene>; <scene name='Turns_in_Proteins/Thermolysin2/2'>Isolated turn</scene> - Unusual because it has two hbonds.
* <scene name='Turns_in_Proteins/Flavodoxin/1'>Flavodoxin</scene>; <scene name='Turns_in_Proteins/Flavodoxin2/1'>Isolated turn</scene>

The inverse γ-turns have mean phi and psi values at residue ''i'' + 1 of -79 and +69, respectively. In their search of 54 proteins Miner-White, et. al. found 61 inverse γ-turns, but only one formed a β-hairpin producing a reversal in the peptide chain.<ref name="Miner" /> Example of an <scene name='Turns_in_Proteins/2sga_inverse/2'>inverse gamma turn</scene> from proteinase A. Compare the structures of a classic and an inverse turns in the two applets below. The direction of rotation of the orange and violet planes with respect to the yellow plane is opposite for the two turns. As a result of this the backbone nitrogens and oxygens of the two turns are mirror images of each other.

{{Clear}}


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 10,11 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 2 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<Structure load='8tln' size='500' frame='true' align='left' caption='Classic gamma turn; Thermolysin (25-27)' scene='Turns_in_Proteins/8tln_classic/6' />
<Structure load='2sga' size='500' frame='true' align='right' caption='Inverse gamma turn; Proteinase A (113-115)' scene='Turns_in_Proteins/2sga_inverse2/6' />
{{Clear}}
==Notes and References==

<references />

Turns in Proteins

2012-08-14T16:07:33Z

Karl Oberholser:

<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/Hemery/4' />__NOTOC__
Turns are classified as a type of secondary structure, but unlike helices and sheets which have ordered, repetitive structures, turns only have ordered structures, but like helices and sheets they can be classified by the values of the torsional angles of the Cα's. This article describes β-turns and γ-turns and illustrates their ordered structures.

== Beta Turns ==
All β-turns contain four residues and are divided into classes based on the range of their [[Psi and Phi Angles|phi and psi]] values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> Most classes have a hydrogen bond between the backbond atoms of residues one(''i'') and four (''i + 3''), and this attraction is the major force maintaining the conformation of the bend in the chain, but in several classes a Pro in the third position (''i + 2'') has the cis configuration which produces a conformation which can not form a hydrogen bond (hbonds).

Seven β-turns are shown as blue traces in myohemerytherin in the scene to the right (<scene name='Turns_in_Proteins/Hemery1/1'>Initial scene</scene>). There are only five blue segments because, in two cases, one β-turn follows another one. Only five of the turns contain hydrogen bonds shown in magenta. As explained in [[Calculate structure]], the '''calculate structure''' command does not detect beta turns which have a Pro in the cis configuration and lack a hbond. Since the command has this limitation, the initial scene was produced by manually selecting and coloring the turns and forming the hbonds. <scene name='Turns_in_Proteins/Calculate_structure/2'>Show</scene> the results of the '''calculate structure''' command.

<blockquote>For reasons explained in the Introduction of [[Calculate structure]], the command to form hbonds of secondary structures was not included in the construction of the above scene, but they can be displayed in any scene by doing the following: click on the Jmol frank, in the main menu click on Console, in the bottom box of the console enter the command: calculate hbonds structure and then click Run.
</blockquote>
<blockquote>Also, if any scene shows the secondary structure and it does not show the beta turns highlighted in blue, the beta turns can be shown in blue by following the above procedure but enter select protein; calculate structure; cartoon; color structure into the bottom box of the console.
</blockquote>

Shown in <scene name='Turns_in_Proteins/Hemery_wf/5'>wireframe</scene> so that one can see the hydrogen bonds are positioned between the first and the fourth residues of the turn and involve backbone atoms. Can you locate the cis configured Pro in the two turns without hbonds? <scene name='Turns_in_Proteins/Rama_2mhr/1'>Ramachandran plot</scene> ([[Ramachandran Plot]]).

{{Clear}}

=== Examples ===
Examples of four of the nine classes<ref name=beta/> of β-turns are shown below with two examples of each of the four classes. The turns were cut from either myohemerytherin (2mhr.pdb) or domain 2 of glycogen phosphorylase chain A (1abb.pdb). Compare the shapes of the turns and observe the differences in the phi (φ) and psi (ψ) values of the second and third residues. Checking the synchronize box will permit you to rotate all the turns by rotating any one of the turns with the mouse.


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 1,2,3,4,5,6,7,8 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 8 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<table style="width:100%;">
<tr align="center">
<th style="width:25%;">Class I
</th>
<th style="width:25%;">Class II
</th>
<th style="width:25%;">Class III
</th>
<th style="width:25%;">Class IV B
</th>
</tr>
<tr align="center">
<td>
<applet load='2mhr 12-15.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_12-15/4' />
</td>

<td>
<applet load='2mhr 114-117.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_114-117/3'/>
</td>
<td>
<applet load='1abb 636-639.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_636-639/1' />
</td>
<td>
<applet load='2mhr 5-8.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_5-8/3'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -66°, ψ = -19°
    Residue 3: φ = -91°, ψ = -1°
</td>
<td>
   Residue 2: φ = -56°, ψ = +126°
    Residue 3: φ = +78°, ψ = +1°
</td>
<td>
   Residue 2: φ = +56°, ψ = -117°
    Residue 3: φ = -125°, ψ = +19°
</td>
<td>
   Residue 2: φ = -135°, ψ = +112°
    Residue 3: φ = -63°, ψ = +163°
</td>
</tr>

<tr align="center">
<td>
<applet load='2mhr 67-70' size='200' frame='false' scene='Turns_in_Proteins/2mhr_67-70/4' />
</td>
<td>
<applet load='1abb 610-613.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_610-613/3' />
</td>
<td>
<applet load='1abb 693-696.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_693-696/2' />
</td>
<td>
<applet load='2mhr 88-91' size='200' frame='false' scene='Turns_in_Proteins/2mhr_88-91/2'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -70°, ψ = -25°
    Residue 3: φ = -109°, ψ = +29°
</td>
<td>
   Residue 2: φ = -53°, ψ = +131°
    Residue 3: φ = +78°, ψ = -10°
</td>
<td>
   Residue 2: φ = +47°, ψ = -122°
    Residue 3: φ = -94°, ψ = +2°
</td>
<td>
   Residue 2: φ = -89°, ψ = +142°
    Residue 3: φ = -76°, ψ = +135°
</td>
</tr>
</table>
<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/2mhr_5-8c/2' />
Turn 2mhr 5-8, classIVB, is shown in the applet on the right. Notice that it does not have a hydrogen bond and that the backbone atoms of the first and fourth residues are not in position to form a hydrogen bond because the presence of a cis peptide bond. (<scene name='Turns_in_Proteins/2mhr_5-8c/2'>Initial scene</scene>) <scene name='Turns_in_Proteins/2mhr_114-117b/2'>Compare</scene> with a turn which has a hbond. The oxygen and nitrogen of the <scene name='Turns_in_Proteins/2mhr_88-91b/2' >cis peptide bond</scene> project from the same edge of the plane, whereas with the trans peptide bonds they project from opposite edges of the plane. The <scene name='Turns_in_Proteins/Rama_8_turns/6'>Ramachandran plot</scene> of the eight turns shown above. Two residues of each turn are plotted giving a total of 16 points. Hover the cursor over a sphere to identify the residue name and number. Realize that, in most cases, the spheres that are of the same class and are close to each other are not part of the same turn. Notice that Gly is the only residue in a [[Ramachandran Plot#Plot regions limited by steric hindrance|disallowed region]] since other residues at those positions could not generate the angles necessary to form the turn and that Pro is the third residue in both class IVB turns.
== Gamma Turns ==
Gamma turns consist of three residues and contain a hydrogen bond between residues one and three. In a search of 54 proteins nine proteins were found to have eleven classic γ-turns, and these eleven turns had mean phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref> Seven of these eleven turns are involved in the formation of β-hairpins which produce a reversal in the peptide chain. Several examples of β-hairpins follow:
* <scene name='Turns_in_Proteins/2alp_classic/3'>Alpha-Lytic protease</scene>; <scene name='Turns_in_Proteins/2alp_classic2/2'>Isolated turn</scene>
* <scene name='Turns_in_Proteins/Proteinase_a/4'>Proteinase A</scene>; <scene name='Turns_in_Proteins/Proteinase_a2/3'>Isolate Turn</scene>
* <scene name='Turns_in_Proteins/Thermolysin/2'>Thermolysin</scene>; <scene name='Turns_in_Proteins/Thermolysin2/2'>Isolated turn</scene> - Unusual because it has two hbonds.
* <scene name='Turns_in_Proteins/Flavodoxin/1'>Flavodoxin</scene>; <scene name='Turns_in_Proteins/Flavodoxin2/1'>Isolated turn</scene>

The inverse γ-turns have mean phi and psi values at residue ''i'' + 1 of -79 and +69, respectively. In their search of 54 proteins Miner-White, et. al. found 61 inverse γ-turns, but only one formed a β-hairpin producing a reversal in the peptide chain.<ref name="Miner" /> Example of an <scene name='Turns_in_Proteins/2sga_inverse/2'>inverse gamma turn</scene> from proteinase A. Compare the structures of a classic and an inverse turns in the two applets below. The direction of rotation of the orange and violet planes with respect to the yellow plane is opposite for the two turns. As a result of this the backbone nitrogens and oxygens of the two turns are mirror images of each other.

{{Clear}}


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 10,11 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 2 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<Structure load='8tln' size='500' frame='true' align='left' caption='Classic gamma turn; Thermolysin (25-27)' scene='Turns_in_Proteins/8tln_classic/6' />
<Structure load='2sga' size='500' frame='true' align='right' caption='Inverse gamma turn; Proteinase A (113-115)' scene='Turns_in_Proteins/2sga_inverse2/6' />
{{Clear}}
==Notes and References==

<references />

Collagen

2012-08-01T18:32:27Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/1'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/1'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a/3'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Collagen

2012-07-18T20:41:15Z

Karl Oberholser:

'''Collagen''', the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. As with all fibrous proteins collagen is, for the most part, characterized by highly repetitive simple sequence. Here we study two model compounds (The structure of [[4clg]]<ref>J.M. Chen, C.E. Kung, S.H. Feairheller, E.M. Brown, AN ENERGETIC EVALUATION OF A "SMITH" COLLAGEN MICROFIBRIL MODEL, J. Protein Chem., '''10''', 535, 1991</ref> is shown in the applet to the right.) for naturally occurring collagen, in order to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to [[Collagen Structure & Function]] for information on the functions and disorders of collagen and a link in the External Links section of this page for assembly movies of the triple helix of types I and IV.

<StructureSection load='4clg' size='500' side='right' caption='Structure of Collagen (PDB entry [[4clg]] or [[1cag]])' scene='Collagen/Opening/4' >__NOTOC__

== Structure of a Segment ==

A fiber segment is made up of 5 tropocollagens, each is shown in a <scene name='Collagen/Fiber_segment/2'>different color</scene>. One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be <scene name='Collagen/Staggered_cut/4'>staggered</scene>. This staggered pattern is produced when the tropocollagens associate to form the fiber segment. The collagen fiber is constructed by connecting the segments together, and the presence of these staggered ends permits the tropocollagens from different segments to form strong attractions adding to the strength of the fiber. Add tropocollagens <scene name='Collagen/Fiber_section_one/2'>one</scene> at a time to form the fiber section, <scene name='Collagen/Fiber_section_two/2'>two</scene>, <scene name='Collagen/Fiber_section_three/3'>three</scene>, <scene name='Collagen/Fiber_section_four/2'>four</scene>, <scene name='Collagen/Fiber_section_five/2'>five</scene>. View fiber segment as <scene name='Collagen/Fiber_section_backbone/4'>backbone only</scene>. Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each <scene name='Collagen/One_tropocollagen/1'>tropocollagen molecule</scene> contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone/1'>backbone</scene> only.
== Lower Levels of Structure ==

=== Primary Structure of Peptide ===
<scene name='Collagen/One_peptide_wireframe/1'>Show side chains</scene> of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Toggling spin off will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model ([[4clg]]) being studied here contains a <scene name='Collagen/One_peptide_tricolored/1'>repeating sequence</scene> of residues - Gly-Pro-Hyp. This sequence produces a conformation which is a <scene name='Collagen/One_peptide_backbone/1'>left-handed helix</scene> with a rise 10.0 Å/turn or <scene name='Collagen/Peptide_3_residue_segments/1'>3.3 residues per turn</scene>, the peptide is colored in three residue segments. <scene name='Collagen/Peptide_helix_z_axis/1'>Looking down</scene> the center axis of a segment of the helix. Since a helix with a larger rise is superimposed on the helix described above, the entire center axis does not align for viewing. The <scene name='Collagen/Ramachandran/2'>Ramachandran plot</scene> shows that the psi and phi angles of the collagen helix are different from the α-helix, which has a rise of 3.6. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of [[Ramachandran_Plots|α-helix]] residues to be located.

=== Other Levels of Structure ===

As shown above tropocollagen is formed by <scene name='Collagen/One_tropocollagen/1'>three peptides</scene> twisting around each other, and in doing so the peptides make <scene name='Collagen/Peptide_3_residue_segments2/2'>one turn every ~7 three-residue repeats</scene> (Cyan colored residues mark the approximate length of one turn.). <scene name='Collagen/One_tropocollagen2/1'>Three cyan colored residues</scene> mark the approximate distance of one turn of the peptides in a tropocollagen. Tropocollagen displayed as <scene name='Collagen/One_tropocollagen_backbone2/1'>backbone only</scene> clearly shows both types of helical turns - the 3.3 residue/turn and ~21 residue/turn.

Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen <scene name='Collagen/Gly_position_tropo/2'>positioned in the center</scene> of the triple helix. The two types of helical turns consistently positions the Gly in the center of the triple helix. Proline and the hydroxyproline are on the <scene name='Collagen/Pros_position_tropo/1'>outside</scene> of the triple helix. With the hydroxyl group of Hyp extending to the surface of the triple helix, it can be involved in hydrogen bond formation, as will be seen in the next section. The cyclical side chains of Pro and Hyp are some what rigid, and this rigidity adds to the stability of the collagen fiber. The primary structure of repeating Gly-Pro-Hyp along with the two types of helical turns determine the 3D positions of Gly, Pro and Hyp in the tropocollagen.

In order to make a compact strong fiber the interior residues of the triple helix need to be close packed. The <scene name='Collagen/Gly_no_hindrance/1'>Gly side chain</scene> is the only one small enough to accommodate this close packing in the interior of the triple helix (realize that in this model the hydrogen on the α carbon is not displayed). <scene name='Collagen/Glys_close_pack/1'>Three Gly</scene>, one on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between these carbons and the atoms of the adjacent Gly. <scene name='Collagen/Glys_pro_close/2'>A Pro</scene> on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding the <scene name='Collagen/Glys_pro_hyp/1'>Hyp</scene> shows that Pro and Hyp are tightly positioned around the small interior Gly leaving no space for side chains longer than the single hydrogen of Gly.

== Maintainance Forces ==

=== Intra-tropocollagen Attractions ===

Intra-tropocollagen attractions are primarily hydrogen bonds formed between the peptides in the triple helix. The three polypeptide chains are <scene name='Collagen/Intra-hbonds/4'>staggered</scene> in position by one residue, that is, a Pro on Chain A is at the same level along the triple helix axis as a Gly on Chain B and a Hyp on Chain C. This staggered arrangement not only <scene name='Collagen/Intra-hbonds2/6'>aligns</scene> a Gly backbone NH (imino group) with a Pro backbone O (carbonyl oxygen) on one of the other peptides but also brings the two groups close enough so that a <scene name='Collagen/Intra-hbonds6/2'>hydrogen bond</scene> can form between the imino hydrogen and the carbonyl oxygen. This alignment occurs with Gly in each of the three peptides so that the Gly imino hydrogens of Chain A form <scene name='Collagen/Hbonds_a_to_b/6'>hydrogen bonds</scene> (orange) with the Pro carbonyl oxygens on Chain B, and likewise Gly of <scene name='Collagen/Hbonds_a_to_b/5'>Chain B to Pro of Chain C</scene> (yellow) and Gly of <scene name='Collagen/Hbonds_c_to_a/1'>Chain C to Pro of Chain A</scene> (green). The force of these hydrogen bonds extending the length of the tropocollagen add up to a strong attractive force which mantain the integrity of the tropocollagen. Since the main chain N atoms of both Pro and Hyp residues lack H atoms, only Gly can provide hydrogen to form these hydrogen bonds.

=== Inter-tropocollagen Attractions ===

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. As shown above, Hyp is the outer most residue on the <scene name='Collagen/Pros_position_tropo/1'>surface</scene> of the triple helix, and the hydroxyl groups are the atoms that extend out the most from the surface. The hydrogen bonds are formed between the hydroxyl hydrogen of a Hyp and a backbone carbonyl oxygen. As the peptides in a tropocollagen twist about each other they come into <scene name='Collagen/Hlite_c_k_peptides/1'>close contact</scene> with particular peptides in adjacent tropocollagens and then move away from them. The two peptide highlighted in spacefill are located in two different tropocollagens. Notice that in this case, they make contact with each other in the middle of the strands, and a hydrogen bond is located at this point of contact. The <scene name='Collagen/Inter-hbonds1/2'>hydrogen bond</scene> consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Another example shows <scene name='Collagen/Hlite_k_o/1'>two peptides</scene> from two different tropocollagens making contact at the ends of the fiber segment, and of course it is within these regions where the inter-tropocollagen attractions occur. At one end a <scene name='Collagen/Inter-hbond2/4'>hydrogen bond</scene> is formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in the second peptide. At the other end of the two peptides a <scene name='Collagen/Inter-hbond3/2'>Hyp carbonyl oxygen</scene> donates its electrons to a Hyp hydroxyl hydrogen. Show the <scene name='Collagen/2nd_view_hbond3/2'>hydrogen bond</scene> in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber. Without the proper amount of vitamin C in their diets humans can not make Hyp, and therefore can not make stable collagen and strong bones.

== Effect of a Mutation ==
The mutation being considered is an Ala replacing a Gly. Synthetic model PDB ID: [[1cag]]<ref>J.BELLA,M.EATON,B.BRODSKY,H.M.BERMAN, CRYSTAL AND MOLECULAR STRUCTURE OF A COLLAGEN-LIKE PEPTIDE AT 1.9 A RESOLUTION. ''SCIENCE'', '''266''', 75, 1994</ref> is <scene name='Collagen/1cag/7'>tropocollagen</scene> whose peptides contain thirty residues and have a <scene name='Collagen/Collagen_chain_1cag/4'>sequence</scene> of (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as {{Template:ColorKey_Element_C}} {{Template:ColorKey_Element_O}} {{Template:ColorKey_Element_N}}). Viewing [[1cag]] from the side of the fiber shows: the <scene name='Collagen/1cag1/1'>Gly</scene> is only partially visible because it is buried in the interior, <scene name='Collagen/1cag2/1'>Pro</scene> being much more visible is positioned closer to the surface, <scene name='Collagen/1cag3/1'>Hyp</scene> being entirely on the surface is clearly visible, and <scene name='Collagen/1cag4/1'>Ala</scene> being a substitute for Gly is only partially visible.

The <scene name='Collagen/1cag_surface/4'>surface</scene> of the tropocollagen is shown with the Ala appearing as olive and the Pro and Hyp adjacent to the Ala appearing as dark brown. Notice that the surface at these Pro and Hyp bulges slightly. This protrusion is due to the fact that the packing about the Ala side chains is not as close as it is about the Gly. In the two side-by-side scenes shown below compare the amount of open space between the chains in the area of the scene center. In the [[1cag]] scene in the area of the Ala the distance between the chains is slightly greater than that of [[4clg]] scene.

</StructureSection>

<table width='100%' align='left' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='4clg' size='400' frame='true' align='left' name='id1' scene='Collagen/Glys_close_wf/1' /></td><td bgcolor='#eeeeee'><Structure load='1cag' size='400' frame='true' align='right' name='id2' scene='Collagen/1cag_ala_pack_wf/1' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Gly Packing in [[4clg]]''' (<scene name='Collagen/Glys_close_wf/1'> Initial scene</scene>)</center></td><td bgcolor='#eeeeee'><center>'''Ala Packing in [[1cag]] (Mutated Collagen)''' (<scene name='Collagen/1cag_ala_pack_wf/1'> Initial scene</scene>)</center></td></tr></table>

__NOTOC__
In order to convince yourself that there is a difference in the interchain distances in the area of the Ala, <scene name='Collagen/1cag_measurements/2'>show distances</scene> between Gly (Ala) and Pro which form intratropocollagen hydrogen bonds. Hydrogen bonds are not formed between Ala and Pro because the distances between the atoms forming the bonds are too great. The absence of the intratropocollagen hydrogen bonds, which is due to replacing Gly with a residue having a longer side chain, disrupts collagen's rope-like structure and is responsible for the symptoms of such human diseases as osteogenesis imperfecta and certain Ehlers-Danlos syndromes.

==3D structures of collagen==

''Update November 2011''

[[3hqv]], [[3hr2]] – Col I – rat – fiber diffraction 
[[1q7d]] - hCol I α1 integrin-binding domain – human 
[[1u5m]] - hCol II α1 (mutant) 
[[3dmw]] - hCol III α1 
[[1li1]] - hCol IV α Nc1 domain 
[[1t60]], [[1t61]], [[1m3d]] - Col IV α Nc1 domain – bovine 
[[1kth]] - hCol III α3 Kunitz type domain 
[[1kun]] - hCol III α3 Kunitz type domain – NMR 
[[2knt]], [[1knt]] - hCol VI Kunitz type domain 
[[1o91]] - mCol VIII α1 Nc1 domain - mouse 
[[2uur]] - hCol IX α1 Nc4 domain 
[[1gr3]] - hCol X α1 Nc1 domain 
[[1b9p]], [[1b9q]] - Col IX α1 Nc4 domain (mutant) 
[[3n3f]] – hCol XIV Nc1 domain 
[[1dy2]] - mCol XV endostatin domain 
[[3hon]], [[3hsh]] - hCol XVIII tetramerization domain 
[[1bnl]] - hCol XVIII C terminal domain 
[[1dy0]], [[1dy1]] - mCol XVIII endostatin domain 
[[2ekj]], [[2ee3]] - hCol XX α1 fn3 domain 
[[2dkm]] - hCol XX α1 fn3 domain - NMR 
[[3ipn]] – Col modified 
[[1wzb]], [[1itt]], [[1k6f]] – Col triple helix 
[[1zpx]], [[1sp7]], [[1sop]] – Col mini – hydra – NMR 
[[2cuo]], [[2d3f]], [[2d3h]], [[2g66]] – Col model peptides

===Collagen complex with binding proteins===

[[3ejh]], [[3gxe]] – hCol I α1 C-terminal + fibronectin 
[[2fse]] – hCol II + MHC HLA-DR1 
[[2seb]] - hCol II + MHC HLA-DR4 
[[2v53]] - hCol III α1 + Sparc 
[[2wuh]] – hCol + discoidin domain receptor 2 
[[1dzi]] – Col + integrin α2 domain 
[[2f6a]] – Col + Col adhesin

==References==

{{Reflist}}

==External Links==
[http://www.mc.vanderbilt.edu/cmb/collagen/ Movies] of assembly of triple helix of type I and IV collagen.

== Contributor ==
Much of the content of this page was taken from an earlier non-Proteopedia version of Collagen which was in large part developed by '''Gretchen Heide Bisbort''', a 1999 graduate of Messiah College.

[[Category:Topic Page]]

Turns in Proteins

2012-06-25T19:58:58Z

Karl Oberholser:

<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/Hemery/4' />__NOTOC__
Turns are classified as a type of secondary structure, but unlike helices and sheets which have ordered, repetitive structures, turns only have ordered structures, but like helices and sheets they can be classified by the values of the torsional angles of the Cα's. This article describes β-turns and γ-turns and illustrates their ordered structures.

== Beta Turns ==
All β-turns contain four residues and are divided into classes based on the range of their [[Psi and Phi Angles|phi and psi]] values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> Most classes have a hydrogen bond between the backbond atoms of residues one(''i'') and four (''i + 3''), and this attraction is the major force maintaining the conformation of the bend in the chain, but in several classes a Pro in the third position (''i + 2'') has the cis configuration which produces a conformation which can not form a hydrogen bond (hbonds).

Seven β-turns are shown as blue traces in myohemerytherin in the scene to the right (<scene name='Turns_in_Proteins/Hemery1/1'>Initial scene</scene>). There are only five blue segments because, in two cases, one β-turn follows another one. Only five of the turns contain hydrogen bonds shown in magenta. As explained in [[Calculate structure]], the '''calculate structure''' command does not detect beta turns which have a Pro in the cis configuration and lack a hbond. Since the command has this limitation, the initial scene was produced by manually selecting and coloring the turns and forming the hbonds. <scene name='Turns_in_Proteins/Calculate_structure/2'>Show</scene> the results of the '''calculate structure''' command.

<blockquote>For reasons explained in the Introduction of [[Calculate structure]], the command to form hbonds of secondary structures was not included in the construction of the above scene, but they can be displayed in any scene by doing the following: click on the Jmol frank, in the main menu click on Console, in the bottom box of the console enter the command: calculate hbonds structure and then click Run.
</blockquote>

Shown in <scene name='Turns_in_Proteins/Hemery_wf/5'>wireframe</scene> so that one can see the hydrogen bonds are positioned between the first and the fourth residues of the turn and involve backbone atoms. Can you locate the cis configured Pro in the two turns without hbonds? <scene name='Turns_in_Proteins/Rama_2mhr/1'>Ramachandran plot</scene> ([[Ramachandran Plot]]).

{{Clear}}

=== Examples ===
Examples of four of the nine classes<ref name=beta/> of β-turns are shown below with two examples of each of the four classes. The turns were cut from either myohemerytherin (2mhr.pdb) or domain 2 of glycogen phosphorylase chain A (1abb.pdb). Compare the shapes of the turns and observe the differences in the phi (φ) and psi (ψ) values of the second and third residues. Checking the synchronize box will permit you to rotate all the turns by rotating any one of the turns with the mouse.


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 1,2,3,4,5,6,7,8 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 8 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<table style="width:100%;">
<tr align="center">
<th style="width:25%;">Class I
</th>
<th style="width:25%;">Class II
</th>
<th style="width:25%;">Class III
</th>
<th style="width:25%;">Class IV B
</th>
</tr>
<tr align="center">
<td>
<applet load='2mhr 12-15.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_12-15/4' />
</td>

<td>
<applet load='2mhr 114-117.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_114-117/3'/>
</td>
<td>
<applet load='1abb 636-639.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_636-639/1' />
</td>
<td>
<applet load='2mhr 5-8.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_5-8/3'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -66°, ψ = -19°
    Residue 3: φ = -91°, ψ = -1°
</td>
<td>
   Residue 2: φ = -56°, ψ = +126°
    Residue 3: φ = +78°, ψ = +1°
</td>
<td>
   Residue 2: φ = +56°, ψ = -117°
    Residue 3: φ = -125°, ψ = +19°
</td>
<td>
   Residue 2: φ = -135°, ψ = +112°
    Residue 3: φ = -63°, ψ = +163°
</td>
</tr>

<tr align="center">
<td>
<applet load='2mhr 67-70' size='200' frame='false' scene='Turns_in_Proteins/2mhr_67-70/4' />
</td>
<td>
<applet load='1abb 610-613.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_610-613/3' />
</td>
<td>
<applet load='1abb 693-696.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_693-696/2' />
</td>
<td>
<applet load='2mhr 88-91' size='200' frame='false' scene='Turns_in_Proteins/2mhr_88-91/2'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -70°, ψ = -25°
    Residue 3: φ = -109°, ψ = +29°
</td>
<td>
   Residue 2: φ = -53°, ψ = +131°
    Residue 3: φ = +78°, ψ = -10°
</td>
<td>
   Residue 2: φ = +47°, ψ = -122°
    Residue 3: φ = -94°, ψ = +2°
</td>
<td>
   Residue 2: φ = -89°, ψ = +142°
    Residue 3: φ = -76°, ψ = +135°
</td>
</tr>
</table>
<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/2mhr_5-8c/2' />
Turn 2mhr 5-8, classIVB, is shown in the applet on the right. Notice that it does not have a hydrogen bond and that the backbone atoms of the first and fourth residues are not in position to form a hydrogen bond because the presence of a cis peptide bond. (<scene name='Turns_in_Proteins/2mhr_5-8c/2'>Initial scene</scene>) <scene name='Turns_in_Proteins/2mhr_114-117b/2'>Compare</scene> with a turn which has a hbond. The oxygen and nitrogen of the <scene name='Turns_in_Proteins/2mhr_88-91b/2' >cis peptide bond</scene> project from the same edge of the plane, whereas with the trans peptide bonds they project from opposite edges of the plane. The <scene name='Turns_in_Proteins/Rama_8_turns/6'>Ramachandran plot</scene> of the eight turns shown above. Two residues of each turn are plotted giving a total of 16 points. Hover the cursor over a sphere to identify the residue name and number. Realize that, in most cases, the spheres that are of the same class and are close to each other are not part of the same turn. Notice that Gly is the only residue in a [[Ramachandran Plot#Plot regions limited by steric hindrance|disallowed region]] since other residues at those positions could not generate the angles necessary to form the turn and that Pro is the third residue in both class IVB turns.
== Gamma Turns ==
Gamma turns consist of three residues and contain a hydrogen bond between residues one and three. In a search of 54 proteins nine proteins were found to have eleven classic γ-turns, and these eleven turns had mean phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref> Seven of these eleven turns are involved in the formation of β-hairpins which produce a reversal in the peptide chain. Several examples of β-hairpins follow:
* <scene name='Turns_in_Proteins/2alp_classic/3'>Alpha-Lytic protease</scene>; <scene name='Turns_in_Proteins/2alp_classic2/2'>Isolated turn</scene>
* <scene name='Turns_in_Proteins/Proteinase_a/4'>Proteinase A</scene>; <scene name='Turns_in_Proteins/Proteinase_a2/3'>Isolate Turn</scene>
* <scene name='Turns_in_Proteins/Thermolysin/2'>Thermolysin</scene>; <scene name='Turns_in_Proteins/Thermolysin2/2'>Isolated turn</scene> - Unusual because it has two hbonds.
* <scene name='Turns_in_Proteins/Flavodoxin/1'>Flavodoxin</scene>; <scene name='Turns_in_Proteins/Flavodoxin2/1'>Isolated turn</scene>

The inverse γ-turns have mean phi and psi values at residue ''i'' + 1 of -79 and +69, respectively. In their search of 54 proteins Miner-White, et. al. found 61 inverse γ-turns, but only one formed a β-hairpin producing a reversal in the peptide chain.<ref name="Miner" /> Example of an <scene name='Turns_in_Proteins/2sga_inverse/2'>inverse gamma turn</scene> from proteinase A. Compare the structures of a classic and an inverse turns in the two applets below. The direction of rotation of the orange and violet planes with respect to the yellow plane is opposite for the two turns. As a result of this the backbone nitrogens and oxygens of the two turns are mirror images of each other.

{{Clear}}


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 10,11 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 2 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<Structure load='8tln' size='500' frame='true' align='left' caption='Classic gamma turn; Thermolysin (25-27)' scene='Turns_in_Proteins/8tln_classic/6' />
<Structure load='2sga' size='500' frame='true' align='right' caption='Inverse gamma turn; Proteinase A (113-115)' scene='Turns_in_Proteins/2sga_inverse2/6' />
{{Clear}}
==Notes and References==

<references />

Turns in Proteins

2012-06-25T19:50:42Z

Karl Oberholser:

<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/Hemery/4' />
Turns are classified as a type of secondary structure, but unlike helices and sheets which have ordered, repetitive structures, turns only have ordered structures, but like helices and sheets they can be classified by the values of the torsional angles of the Cα's. This article describes β-turns and γ-turns and illustrates their ordered structures.

== Beta Turns ==
All β-turns contain four residues and are divided into classes based on the range of their [[Psi and Phi Angles|phi and psi]] values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> Most classes have a hydrogen bond between the backbond atoms of residues one(''i'') and four (''i + 3''), and this attraction is the major force maintaining the conformation of the bend in the chain, but in several classes a Pro in the third position (''i + 2'') has the cis configuration which produces a conformation which can not form a hydrogen bond (hbonds).

Seven β-turns are shown as blue traces in myohemerytherin in the scene to the right (<scene name='Turns_in_Proteins/Hemery1/1'>Initial scene</scene>). There are only five blue segments because, in two cases, one β-turn follows another one. Only five of the turns contain hydrogen bonds shown in magenta. As explained in [[Calculate structure]], the '''calculate structure''' command does not detect beta turns which have a Pro in the cis configuration and lack a hbond. Since the command has this limitation, the initial scene was produced by manually selecting and coloring the turns and forming the hbonds. <scene name='Turns_in_Proteins/Calculate_structure/2'>Show</scene> the results of the '''calculate structure''' command.

<blockquote>For reasons explained in the Introduction of [[Calculate structure]], the command to form hbonds of secondary structures was not included in the construction of the above scene, but they can be displayed in any scene by doing the following: click on the Jmol frank, in the main menu click on Console, in the bottom box of the console enter the command: calculate hbonds structure and then click Run.
</blockquote>

Shown in <scene name='Turns_in_Proteins/Hemery_wf/5'>wireframe</scene> so that one can see the hydrogen bonds are positioned between the first and the fourth residues of the turn and involve backbone atoms. Can you locate the cis configured Pro in the two turns without hbonds? <scene name='Turns_in_Proteins/Rama_2mhr/1'>Ramachandran plot</scene> ([[Ramachandran Plot]]).

{{Clear}}

=== Examples ===
Examples of four of the nine classes<ref name=beta/> of β-turns are shown below with two examples of each of the four classes. The turns were cut from either myohemerytherin (2mhr.pdb) or domain 2 of glycogen phosphorylase chain A (1abb.pdb). Compare the shapes of the turns and observe the differences in the phi (φ) and psi (ψ) values of the second and third residues. Checking the synchronize box will permit you to rotate all the turns by rotating any one of the turns with the mouse.


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 1,2,3,4,5,6,7,8 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 8 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<table style="width:100%;">
<tr align="center">
<th style="width:25%;">Class I
</th>
<th style="width:25%;">Class II
</th>
<th style="width:25%;">Class III
</th>
<th style="width:25%;">Class IV B
</th>
</tr>
<tr align="center">
<td>
<applet load='2mhr 12-15.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_12-15/4' />
</td>

<td>
<applet load='2mhr 114-117.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_114-117/3'/>
</td>
<td>
<applet load='1abb 636-639.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_636-639/1' />
</td>
<td>
<applet load='2mhr 5-8.pdb' size='200' frame='false' scene='Turns_in_Proteins/2mhr_5-8/3'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -66°, ψ = -19°
    Residue 3: φ = -91°, ψ = -1°
</td>
<td>
   Residue 2: φ = -56°, ψ = +126°
    Residue 3: φ = +78°, ψ = +1°
</td>
<td>
   Residue 2: φ = +56°, ψ = -117°
    Residue 3: φ = -125°, ψ = +19°
</td>
<td>
   Residue 2: φ = -135°, ψ = +112°
    Residue 3: φ = -63°, ψ = +163°
</td>
</tr>

<tr align="center">
<td>
<applet load='2mhr 67-70' size='200' frame='false' scene='Turns_in_Proteins/2mhr_67-70/4' />
</td>
<td>
<applet load='1abb 610-613.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_610-613/3' />
</td>
<td>
<applet load='1abb 693-696.pdb' size='200' frame='false' scene='Turns_in_Proteins/1abb_693-696/2' />
</td>
<td>
<applet load='2mhr 88-91' size='200' frame='false' scene='Turns_in_Proteins/2mhr_88-91/2'/>
</td>
</tr>
<tr>
<td>
   Residue 2: φ = -70°, ψ = -25°
    Residue 3: φ = -109°, ψ = +29°
</td>
<td>
   Residue 2: φ = -53°, ψ = +131°
    Residue 3: φ = +78°, ψ = -10°
</td>
<td>
   Residue 2: φ = +47°, ψ = -122°
    Residue 3: φ = -94°, ψ = +2°
</td>
<td>
   Residue 2: φ = -89°, ψ = +142°
    Residue 3: φ = -76°, ψ = +135°
</td>
</tr>
</table>
<Structure load='2mhr' size='500' frame='true' align='right' caption='' scene='Turns_in_Proteins/2mhr_5-8c/2' />
Turn 2mhr 5-8, classIVB, is shown in the applet on the right. Notice that it does not have a hydrogen bond and that the backbone atoms of the first and fourth residues are not in position to form a hydrogen bond because the presence of a cis peptide bond. (<scene name='Turns_in_Proteins/2mhr_5-8c/2'>Initial scene</scene>) <scene name='Turns_in_Proteins/2mhr_114-117b/2'>Compare</scene> with a turn which has a hbond. The oxygen and nitrogen of the <scene name='Turns_in_Proteins/2mhr_88-91b/2' >cis peptide bond</scene> project from the same edge of the plane, whereas with the trans peptide bonds they project from opposite edges of the plane. The <scene name='Turns_in_Proteins/Rama_8_turns/6'>Ramachandran plot</scene> of the eight turns shown above. Two residues of each turn are plotted giving a total of 16 points. Hover the cursor over a sphere to identify the residue name and number. Realize that, in most cases, the spheres that are of the same class and are close to each other are not part of the same turn. Notice that Gly is the only residue in a [[Ramachandran Plot#Plot regions limited by steric hindrance|disallowed region]] since other residues at those positions could not generate the angles necessary to form the turn and that Pro is the third residue in both class IVB turns.
== Gamma Turns ==
Gamma turns consist of three residues and contain a hydrogen bond between residues one and three. In a search of 54 proteins nine proteins were found to have eleven classic γ-turns, and these eleven turns had mean phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref> Seven of these eleven turns are involved in the formation of β-hairpins which produce a reversal in the peptide chain. Several examples of β-hairpins follow:
* <scene name='Turns_in_Proteins/2alp_classic/3'>Alpha-Lytic protease</scene>; <scene name='Turns_in_Proteins/2alp_classic2/2'>Isolated turn</scene>
* <scene name='Turns_in_Proteins/Proteinase_a/4'>Proteinase A</scene>; <scene name='Turns_in_Proteins/Proteinase_a2/3'>Isolate Turn</scene>
* <scene name='Turns_in_Proteins/Thermolysin/2'>Thermolysin</scene>; <scene name='Turns_in_Proteins/Thermolysin2/2'>Isolated turn</scene> - Unusual because it has two hbonds.
* <scene name='Turns_in_Proteins/Flavodoxin/1'>Flavodoxin</scene>; <scene name='Turns_in_Proteins/Flavodoxin2/1'>Isolated turn</scene>

The inverse γ-turns have mean phi and psi values at residue ''i'' + 1 of -79 and +69, respectively. In their search of 54 proteins Miner-White, et. al. found 61 inverse γ-turns, but only one formed a β-hairpin producing a reversal in the peptide chain.<ref name="Miner" /> Example of an <scene name='Turns_in_Proteins/2sga_inverse/2'>inverse gamma turn</scene> from proteinase A. Compare the structures of a classic and an inverse turns in the two applets below. The direction of rotation of the orange and violet planes with respect to the yellow plane is opposite for the two turns. As a result of this the backbone nitrogens and oxygens of the two turns are mirror images of each other.

{{Clear}}


<jmol>
<jmolCheckbox>
<target>all</target>
<scriptWhenChecked>set syncMouse on;sync 10,11 on; </scriptWhenChecked>
<scriptWhenUnchecked>sync * off;</scriptWhenUnchecked>
<text>Synchronize the 2 models for rotation with the mouse. </text>
</jmolCheckbox>
</jmol>
To re-align the models, reload this page.

<Structure load='8tln' size='500' frame='true' align='left' caption='Classic gamma turn; Thermolysin (25-27)' scene='Turns_in_Proteins/8tln_classic/6' />
<Structure load='2sga' size='500' frame='true' align='right' caption='Inverse gamma turn; Proteinase A (113-115)' scene='Turns_in_Proteins/2sga_inverse2/6' />
{{Clear}}
==Notes and References==

<references />

Calculate structure

2012-06-25T15:25:19Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/4'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/7'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/3'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/4'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/7'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/3'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin above. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 

* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/9'>segments in isolation</scene>. (Remember the hbonds can be displayed by running ''calculate hbonds structure'' from the console.) See summary below for a description of each of these T segments. All of these single residue segments are part of turns which are also involved in helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/6'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns.

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-25T15:10:56Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/4'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/7'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/3'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/4'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/7'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/3'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin above. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 

* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/9'>segments in isolation</scene>. (Remember the hbonds can be displayed by running ''calculate hbonds structure'' from the console.) See summary below for a description of each of these T segments. All of these single residue segments are part of turns which are also involved in helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-23T20:25:00Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/4'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/7'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/3'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/4'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/7'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/3'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin above. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 

* <scene name='Calculate_structure/Domain_2_3turns2/7'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. All of these single residue segments are part of turns which are also involved in helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-21T19:54:27Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/4'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/7'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/3'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/4'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/7'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/3'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin above. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 

* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. All of these single residue segments are part of turns which are also involved in helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-21T19:37:03Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/4'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/7'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/3'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/4'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/7'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/3'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin above. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 
If the applet is not running the signed ver. 12 of Jmol, connect with it as you did above, and then click on the above green link. 
After clicking on the above green link, open the console and run the script: <center>select protein; calculate structure; cartoon; color structure; calculate hbonds structure</center> 
* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. The only turns that these single residue segments are part of are involved helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-21T19:26:13Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/4'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/7'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/2'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/4'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/7'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/2'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin below. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 
If the applet is not running the signed ver. 12 of Jmol, connect with it as you did above, and then click on the above green link. 
After clicking on the above green link, open the console and run the script: <center>select protein; calculate structure; cartoon; color structure; calculate hbonds structure</center> 
* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. The only turns that these single residue segments are part of are involved helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-21T19:05:08Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turn classes VIa1, VIa2, and VIb (Do not contain hydrogen bonds.) can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
Since hbonds are deleted by clicking a subsequent green link, ''calculate hbonds structure'' has to be run from the Jmol console, as described above, after every green link click in order to display hbonds. The display of hbonds can be helpful in identifying turns.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/3'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/6'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/2'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/3'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/6'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/2'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin below. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 
If the applet is not running the signed ver. 12 of Jmol, connect with it as you did above, and then click on the above green link. 
After clicking on the above green link, open the console and run the script: <center>select protein; calculate structure; cartoon; color structure; calculate hbonds structure</center> 
* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. The only turns that these single residue segments are part of are involved helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-21T18:17:13Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does an objective identification of these secondary structures. ''Calculate structure'' by itself only identifies the different secondary structures and does not result in the display of a structure. Additional commands are required to color and render the secondary structures differentially and to display the hydrogen bonds (hbonds). The development of the scenes in this article included the use of the script ''select protein; calculate structure; cartoon; color structure''. Since the post-green link processing of the ''calculate hbonds structure'' command is malfunctioning, it was not used when making the scenes. In order to display hbonds in any scene which does not show them, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the command ''calculate hbonds structure'' and then click ''Run''. This same technique, with the exception of entering select protein; calculate structure; cartoon; color structure; calculate hbonds structure into the lower console box, can be used to do an objective identification of the secondary structures on any Proteopedia page in which it has not been done.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turns VIa1, VIa2, and VIb can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
The user is urged to use the above directions to open Jmol version 12 and to run the ''calculate structure'' and the accompanying commands so that the resulting display can be compared with the summary below. Without displaying the images generated by ''calculate structure'' and ''calculate hbonds structure'' the activities and comparisons described below can not be performed. Unless a green link is designed to change the color and structural representation, these two display parameters do not change after they have been set by ''calculate structure'', but all hbonds are deleted by clicking a green link so ''calculate hbonds structure'' has to be run from the console after every green link click in order to display hbonds.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/3'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/6'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/2'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/3'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/6'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/2'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin below. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 
If the applet is not running the signed ver. 12 of Jmol, connect with it as you did above, and then click on the above green link. 
After clicking on the above green link, open the console and run the script: <center>select protein; calculate structure; cartoon; color structure; calculate hbonds structure</center> 
* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. The only turns that these single residue segments are part of are involved helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Calculate structure

2012-06-21T16:36:30Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does a more detailed identification of these secondary structures. (For this detail go to [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]].) Calculate structure by itself only identifies the secondary structural components. Additional commands are required to display the secondary structures and the hbonds. In order to display this detailed information on any Proteopedia page which does not display it, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the commands: select protein; calculate structure; cartoon; color structure; calculate hbonds structure and then click ''Run''.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turns VIa1, VIa2, and VIb can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
The user is urged to use the above directions to open Jmol version 12 and to run the ''calculate structure'' and the accompanying commands so that the resulting display can be compared with the summary below. Without displaying the images generated by ''calculate structure'' and ''calculate hbonds structure'' the activities and comparisons described below can not be performed. Unless a green link is designed to change the color and structural representation, these two display parameters do not change after they have been set by ''calculate structure'', but all hbonds are deleted by clicking a green link so ''calculate hbonds structure'' has to be run from the console after every green link click in order to display hbonds.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/6'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/3'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/6'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/2'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/3'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/6'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/6'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/2'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin below. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 
If the applet is not running the signed ver. 12 of Jmol, connect with it as you did above, and then click on the above green link. 
After clicking on the above green link, open the console and run the script: <center>select protein; calculate structure; cartoon; color structure; calculate hbonds structure</center> 
* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. The only turns that these single residue segments are part of are involved helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Sheets in Proteins

2012-06-21T16:11:27Z

Karl Oberholser:

<Structure load='Silk 64.mol' size='500' frame='true' align='right' caption='Structures of Sheets' scene='Sheets_in_Proteins/Syn_sheet1/2' />
A β-pleated sheet contains multiple peptide strands that are positioned adjacent to one another as the one shown on the right<ref>This model was hand constructed using HyperChem and setting all phi and psi values to -139° and 135°, respectively.</ref> (<scene name='Sheets_in_Proteins/Syn_sheet1/2'> (Initial scene)</scene>). The planes of the <scene name='Sheets_in_Proteins/Syn_sheet2/2'>pleats</scene> are formed by the planes of the peptide bond. The alpha carbons of the peptide chain are at the valleys and peaks of the pleats. The peptides are <scene name='Sheets_in_Proteins/Syn_sheet3/3'>rainbow colored</scene> (blue amino end changing to red carboxy end) to show that the adjacent peptides are running in opposite directions making the sheet antiparallel. Another way of detecting the <scene name='Sheets_in_Proteins/Syn_sheet7/1'>antiparallel sheet</scene> is by displaying as cartoon. The adjacent chains align so that <scene name='Sheets_in_Proteins/Syn_sheet4/1'>hydrogen bonds</scene> are formed between the imino hydrogens of one chain and the carbonyl oxygens of an adjacent chain. These hydrogen bonds provide the major attractive force which maintains the sheet structure. Phi and psi values that permit this alignment in antiparallel sheets have <scene name='Sheets_in_Proteins/Syn_sheet5/1'>median values</scene> of -139° and +135°, respectively. The median values for a parallel sheet are -119° and +113°.

Twisted sheets are found in globular proteins. Unlike the <scene name='Sheets_in_Proteins/Syn_sheet6/2'>above two types</scene> of sheets, the valleys and the peaks of a <scene name='Sheets_in_Proteins/Gly_phosyl2/2'>twisted sheet</scene><ref>This sheet is part of the structure of domain 2 of glycogen phosphorylase (PDB code [[1abb]]).</ref> do not fall on parallel lines. Observe that the sheet is <scene name='Sheets_in_Proteins/Gly_phosyl/4'>parallel</scene>, and showing <scene name='Sheets_in_Proteins/Gly_phosyl3/1'>hydrogen bonds</scene>. Notice that in contrast to the hydrogen bonds of the antiparallel sheet shown above where the bonds were parallel here the bonds are diagonal to each other. Show <scene name='Sheets_in_Proteins/Gly_phosyl5/2'>phi and psi values</scene> for randomly chosen residues. There are a wide range of values for both phi and psi, -108° to -142° and +96° to +148°, respectively. The above sheet shown in the context of <scene name='Sheets_in_Proteins/Gly_phosyl/5'>domain 2</scene> of glycogen phosphorylase. An examples of <scene name='Sheets_in_Proteins/1dtg1/2'>antiparallel twisted sheet</scene><ref>These sheets are part of the structure of human transferrin n-lobe mutant (PDB code [[1dtg]]).</ref>. Showing only the <scene name='Sheets_in_Proteins/1dtg2/2'>sheets</scene>, and with <scene name='Sheets_in_Proteins/1dtg3/1'>hydrogen bonds</scene>. <scene name='Sheets_in_Proteins/1dtg4/3'> Values</scene> of phi and psi for randomly chosen residues; these values range from -98° to -178° and from +90° to +167°, respectively. These ranges overlap the values for the twisted parallel showing that there is no differences in the ranges for the two types of twisted sheets. Median values for phi and psi are -125° and +140°, respectively.

{{Clear}}

== Notes and References ==
<references/>

Sheets in Proteins

2012-06-21T16:01:00Z

Karl Oberholser:

<Structure load='Silk 64.mol' size='500' frame='true' align='right' caption='Structures of Sheets' scene='Sheets_in_Proteins/Syn_sheet1/2' />
A β-pleated sheet contains multiple peptide strands that are positioned adjacent to one another as the one shown on the right<ref>This model was hand constructed using HyperChem and setting all phi and psi values to -139° and 135°, respectively.</ref> (<scene name='Sheets_in_Proteins/Syn_sheet1/2'> (Initial scene)</scene>). The planes of the <scene name='Sheets_in_Proteins/Syn_sheet2/2'>pleats</scene> are formed by the planes of the peptide bond. The alpha carbons of the peptide chain are at the valleys and peaks of the pleats. The peptides are <scene name='Sheets_in_Proteins/Syn_sheet3/3'>rainbow colored</scene> (blue amino end changing to red carboxy end) to show that the adjacent peptides are running in opposite directions making the sheet antiparallel. Another way of detecting the <scene name='Sheets_in_Proteins/Syn_sheet7/1'>antiparallel sheet</scene> is by displaying as cartoon. The adjacent chains align so that <scene name='Sheets_in_Proteins/Syn_sheet4/1'>hydrogen bonds</scene> are formed between the imino hydrogens of one chain and the carbonyl oxygens of an adjacent chain. These hydrogen bonds provide the major attractive force which maintains the sheet structure. Phi and psi values that permit this alignment in antiparallel sheets have <scene name='Sheets_in_Proteins/Syn_sheet5/1'>median values</scene> of -139° and +135°, respectively. The median values for a parallel sheet are -119° and +113°.

Twisted sheets are found in globular proteins. Unlike the <scene name='Sheets_in_Proteins/Syn_sheet6/2'>above two types</scene> of sheets, the valleys and the peaks of a <scene name='Sheets_in_Proteins/Gly_phosyl2/2'>twisted sheet</scene><ref>This sheet is part of the structure of domain 2 of glycogen phosphorylase (PDB code [[1abb]]).</ref> do not fall on parallel lines. Observe that the sheet is <scene name='Sheets_in_Proteins/Gly_phosyl/4'>parallel</scene>, and showing <scene name='Sheets_in_Proteins/Gly_phosyl3/1'>hydrogen bonds</scene>. Notice that in contrast to the hydrogen bonds of the antiparallel sheet shown above where the bonds were parallel here the bonds are diagonal to each other. Show <scene name='Sheets_in_Proteins/Gly_phosyl5/2'>phi and psi values</scene> for randomly chosen residues. There are a wide range of values for both phi and psi, -108° to -142° and +96° to +148°, respectively. The above sheet shown in the context of <scene name='Sheets_in_Proteins/Gly_phosyl/5'>domain 2</scene> of glycogen phosphorylase. An examples of <scene name='Sheets_in_Proteins/1dtg1/1'>antiparallel twisted sheet</scene><ref>These sheets are part of the structure of human transferrin n-lobe mutant (PDB code [[1dtg]]).</ref>. Showing only the <scene name='Sheets_in_Proteins/1dtg2/2'>sheets</scene>, and with <scene name='Sheets_in_Proteins/1dtg3/1'>hydrogen bonds</scene>. <scene name='Sheets_in_Proteins/1dtg4/3'> Values</scene> of phi and psi for randomly chosen residues; these values range from -98° to -178° and from +90° to +167°, respectively. These ranges overlap the values for the twisted parallel showing that there is no differences in the ranges for the two types of twisted sheets. Median values for phi and psi are -125° and +140°, respectively.

{{Clear}}

== Notes and References ==
<references/>

Calculate structure

2012-06-21T15:23:53Z

Karl Oberholser:

An important part of protein structure is the [[secondary structure]] which is made up of [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]], and Jmol has always been capable of determining and displaying these three types of structures with limitations as described in [[Secondary_structure#How Jmol Determines Secondary Structure | How Jmol Determines Secondary Structure ]]. The ''calculate structure''<ref name="calculate">A detailed description is at [http://chemapps.stolaf.edu/jmol/docs/#calculate].</ref> is a command which has been more recently developed and does a more detailed identification of these secondary structures. (For this detail go to [[Helices in Proteins|helices]], [[Sheets in Proteins|sheets]] and [[Turns in Proteins|turns]].) Calculate structure by itself only identifies the secondary structural components. Additional commands are required to display the secondary structures and the hbonds. In order to display this detailed information on any Proteopedia page which does not display it, click on the ''Jmol frank'', in the ''main menu'' click on ''Console'', in the bottom box of the console enter the commands: select protein; calculate structure; cartoon; color structure; calculate hbonds structure and then click ''Run''.

The objectives of this article are:
* Describe briefly how ''calculate structure'' identifies secondary structures, with a focus on identification of β and γ-turns.
* Summarize the observations obtained from using ''calculate structure '' to identify turns in two proteins.

Myohemoerythrin is shown in the applet below. (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)

== ==

<StructureSection load='2mhr.pdb' size='500' side='right' caption='' scene='Calculate_structure/Erythrin/2'>__NOTOC__
=== Basis of Secondary Structure Determination ===

''Calculate structure'' is based on Defined Secondary Structure of Protein (DSSP), a program written in Pascal.<ref name="DSSP">W. Kabsch & C. Sanders, ''Biopolymers'', '''22''', 2577-2636, 1983.</ref> The secondary structure recognition algorithms used in DSSP are based mainly on hydrogen-bonding patterns along with some geometric structures , such as bends. There are two different hydrogen-bonding patterns which are recognized. The one determines the value of n in the expression ''i'' + ''n'' (''i'' is a residue that forms a hydrogen bond with a residue n residues removed from residue ''i''.) where n = 3, 4 or 5. These values define three types of turns. A peptide segment that has repeating turns of the same type are called 310-helix, α-helix, or Π-helix, respectively. If the turn is isolate, it is simply called an n-turn. The other recognized pattern is a hydrogen bond which is between residues which are not close together in sequence. This type of hydrogen bond is called a bridge. Kabsch & Sanders define a ladder as a "set of one or more consecutive bridges of identical type" and a sheet as a "set of one or more ladders connected by shared residues"<ref name="DSSP" />. Bends are peptide segments with high curvature, and the determination of curvature involves torsional angles of the Cα. Bends can overlap with helices and turns.

The results of the ''calculate structure'' computation are printed in the upper box of the console. One part of that output is a summary which identifies peptide segments according to their type of secondary structure with each type having a one letter identifier. During the DSSP analysis it is possible for a residue or a segment of residues to be assigned more than one structural type, so the structural types are assigned a priority. (The summary for myohemerytherin (2mhr) is given below with a key for the one letter identifiers which are rank ordered in decreasing priority.) Turns (T) have a lower priority than sheets of helices with bends (S) having the lowest priority. The helices and sheets which are identified on the summary can easily be associated with the corresponding structures in the applet, but the turns need some additional explanation.

=== Relationship to β and γ Turns ===
The DSSP determination of helices and β-sheets is in agreement with the generally accepted view of these two structures, but the DSSP determination of turns is not as specific as the generally accepted definition of turns. As described above DSSP identifies turns that have 4, 5, or 6 residues with a backbone hbond being present between the first and the last residues. The presence of the hbond is a requirement to be classified as a turn. [[Psi and Phi Angles|Phi and psi torsional angles]] of the Cα are not used by the DSSP procedure to identify n-turns, but the generally accepted definitions of β and γ turns involve these angles.

[[Turns_in_Proteins#Beta Turns|β-turns]] contain four residues and therefore are 3-turns found by DSSP. The classes of β-turns are defined by the range of psi and phi values for the second and third residues.<ref name=beta>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?doc=TRUE&pdbcode=n/a&template=doc_p_bturns.html Characteristics of β-turn classes]</ref> β-turns often have a hbond between residues one and four (''i'' + 3), but there is not an absolute requirement for a hbond. In three classes (VIa1, VIa2, VIb) a Pro in the third position has the cis configuration which does not permit the formation of a hbond ([[Turns_in_Proteins#Beta Turns|View display of structure.]]). The turns in these three classes are not detected by DSSP since they do not contain a hbond.

[[Turns_in_Proteins#Gamma Turns|γ-turns]] contain three residues having a hbond between residues ''i'' and ''i'' + 2 and therefore are not included among the turns found by DSSP. The classic γ-turns have phi and psi values at residue ''i'' + 1 of +75.0 and -64, respectively, and the inverse γ-turns have phi and psi values at residue ''i'' + 1 of -79 and +69, respectively.<ref name="Miner">Miner-White, EJ, et. al. ''One type of gamma turn, rather than the other, gives rise to chain reversal in proteins''. J. Mol. Bio. '''204''', 1983, pp. 777-782.</ref>

===Summary of observations obtained from using ''Calculate structure''===
The following bullet points summarize the results given in the upper console box and the applet display after ''Calculate structure'' and "calculate hbonds structure" were used to identify the turns in myohemerthyrin and Domain 2 of chain A Glycogen Phosphorylase. The nature of the T: segments (turns) reported in the console summary and the pattern of blue colored trace segments in the displayed structure are the focus of the summary.

* Most T segments in the summary contain one or two residues but a few contain three or four residues. With isolated turns DSSP reports two, three and four residues for 3-, 4-, and 5-turns, respectively. If the turn is overlapping with a structure of higher priority fewer residues will be included in the segment.
* The presence of a one-residue T segments in the summary indicates that the β-turn overlaps a structure of higher priority (most often a helix). These single blue colored residues can be at the end or interior of the helix, and some in the interior of a helix may not be colored blue (Domain 2 of chain A Glycogen Phosphorylase).
* All two-residue T segments indicate β-turns. The turns are often part of an helix, as many as three of the four residues can have the color of the helix. Isolated β-turns have two to three residues colored blue in the structure, rarely four.
* T segments that have more than two residues indicate two contiguous or nested β-turns, β-turn nested in a 4- or 5-turn, isolated or nested 4 or 5-turns.
* After ''calculate structure'' and ''calculate hbonds structure'' has been run the following methods can be used to identify the different types of turns. Blue coloration and the hbond bond between ''i'' and ''i'' + 3 can be used to identify overlapping and isolated β-turns. The 4- or 5-turns which are nested in some way are easily identified by residue ''i'' being involved in at least two hbonds. β-turns VIa1, VIa2, and VIb can be identified by locating a trace that has the appearance of a β-turns and is not colored blue and checking for a cis-Pro at ''i + 2''. (Hover the cursor over the trace to display the name and number of the residues.) Also, the values for phi and psi angles at ''i + 1'' and ''i + 2'' can be [[Psi and Phi Angles|determined]] and compared to the values expected for classes VIa1, VIa2, and VIb.<ref name=beta />

=== Illustrations ===
The user is urged to use the above directions to open Jmol version 12 and to run the ''calculate structure'' and the accompanying commands so that the resulting display can be compared with the summary below. Without displaying the images generated by ''calculate structure'' and ''calculate hbonds structure'' the activities and comparisons described below can not be performed. Unless a green link is designed to change the color and structural representation, these two display parameters do not change after they have been set by ''calculate structure'', but all hbonds are deleted by clicking a green link so ''calculate hbonds structure'' has to be run from the console after every green link click in order to display hbonds.

'''Myohemerytherin''' (<scene name='Calculate_structure/Erythrin/2'>Restore initial scene</scene>)
* There are two T segments that contain one residue, <scene name='Calculate_structure/Turn_84/2'>T : A:86_A:86</scene> (β-turn 84-87; 84 & 85 are part of a helix, 86 is colored blue & 87 is white.) and <scene name='Calculate_structure/Turn_110/3'>T : A:110_A:110</scene> (β-turn 110-113; 110 is blue, 111-113 are part of a 310-helix.).
* There are two T segments that contain two residues, <scene name='Calculate_structure/Turn_63/3'>T : A:65_A:66</scene> (β-turn 63-66; 63 & 64 part of a helix, 65 & 66 are blue.) and <scene name='Calculate_structure/Turn_67/6'>T : A:68_A:69</scene> (β-turn 67-70; 70 is part of a helix, 67 & 68 are white & blue, 69 entirely blue.).
* The last T is a three residue segment, <scene name='Calculate_structure/Turn_114/2'>T : A:115_A:117</scene> (β-turn 114-117, 4-turn 114-118; 114 is part of a 310-helix, 115-117 & part of 118 are blue, 118 is partially white.). A β-turn is nested in a 4-turn.
* Can you locate the two turns that are not colored with blue traces and do not contain a hbond between the first and the last residues of the turn. There are two class VIb β-turns in myohemerytherin.

'''Summary for Myohemerytherin:''' 
G : A:12_A:14 
H : A:19_A:37 
H : A:41_A:64 
T : A:65_A:66   <scene name='Calculate_structure/Turn_63/3'>Display beta-turn</scene> 
T : A:68_A:69   <scene name='Calculate_structure/Turn_67/6'>Display beta-turn</scene>; 
H : A:70_A:85 
T : A:86_A:86   <scene name='Calculate_structure/Turn_84/2'>Display beta-turn</scene> 
H : A:93_A:109 
T : A:110_A:110   <scene name='Calculate_structure/Turn_110/2'>Display beta-turn</scene> 
G : A:111_A:114 
T : A:115_A:117   <scene name='Calculate_structure/Turn_114/2'>Display turns</scene> 
Key - '''H''': α-helix; '''B''': β-bridge; '''E''': β-strand; '''G''': 310-helix; '''I''': π-helix; '''T''': 3-, 4-, 5-turn; '''S''': bend. 

=== Identify turns using resourses at RCSB ===
There are two resources at RCSB Protein Data Bank<ref name="RCSB">[http://www.pdb.org/pdb/home/home.do Open home page of PDB]</ref> that can be useful when analyzing the turns or any secondary structures of a protein. After going to the PDB site and selecting your protein of interest by entering the PDB ID or name of the protein, click on the Sequence tab. First one, clicking on 'Sequence & DSSP' under the Chain A heading opens in a separate window the sequence and secodary structures of chain A of the protein. Second one, in the 'Sequence & Structure Relationships' box click on 'Enable Jmol to view annotations in 3D' and then 'Display Jmol'. The Jmol applet remains on top as you scroll down to the annotated sequence. Clicking on a secondary structure in the DSSP bar results in that structure being high lighted in the Jmol applet. The turns that are identified as having only one residue are not shown on the DSSP bar, but if you hoover the cursor over the DSSP bar in the area of that one residue a label will appear identifying the turn, and then if you click the mouse the one residue turn will appear in the Jmol applet. If secondary structure annotations other than DSSP are used, β-turns classes VIa1, VIa2, and VIb may be identified, see myohemerytherin below. If you select one of the other annotations of secondary structure, you will discover that class VIb β-turns are among the structures being annotated. Use end note to open necessary sites.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=2MHR&params.showJmol=true Open myohemerytherin at sequence page with Jmol open];   [http://www.pdb.org/pdb/explore/sequenceText.do?structureId=2MHR&chainId=A Open sequence and Secondary structure page]</ref>

=== Domain 2 of chain A Glycogen Phosphorylase ===
<scene name='Calculate_structure/Domain_2/5'>Load Structure</scene> 
If the applet is not running the signed ver. 12 of Jmol, connect with it as you did above, and then click on the above green link. 
After clicking on the above green link, open the console and run the script: <center>select protein; calculate structure; cartoon; color structure; calculate hbonds structure</center> 
* <scene name='Calculate_structure/Domain_2_3turns2/6'>High light</scene> each of the one residue T segments (''e.g.'' T : A:488_A:488) in the summary below along with a few residues on each side of the single residue. Improve the view by displaying these <scene name='Calculate_structure/Domain_2_3turns3/8'>segments in isolation</scene>. (Remember to display the hbonds by running ''calculate hbonds structure'' from the console.) Only one segment has a residue colored blue, and the other residues are colored as being part of a helix or sheet. See summary below for a description of each of these T segments. The only turns that these single residue segments are part of are involved helices.
* Reveal the nature of the <scene name='Calculate_structure/Domain_2_4turn/2'>remaining T segments</scene>. Displaying these <scene name='Calculate_structure/Domain_2_4turn2/5'>turns in isolation</scene> makes it easier to observe the hbonds. Inspecting them for hbonds (after running ''calculate hbonds structure'' from the console) reveals that all but one of these T segments are part of β-turns with the β-turns overlapping at two locations, and that segment T: 822-825 is part of a 4-turn and two 5-turns. All but two of the segments have at least one residue colored blue (Nitrogens involved in hbonds are also colored blue for ease of identifying the atoms involved in the hbonds.).

'''Summary of T's for Domain 2 of Chain A Glycogen Phosphorylase:'''(All other segments deleted.) 
T : A:488_A:488    488 (colored blue) is between a sheet & 310-helix. 
T : A:495_A:495    495 is at the end of α-helix. 
T : A:525_A:526   β-turn 524-527; first three residues are part of a helix with 527 partially colored blue. 
T : A:594_A:595   β-turn 593-596; 594 & 595 are colored blue, 593 is end of a sheet. 
T : A:611_A:612   β-turn 610-613; 611 & 612 are colored blue, other two are white. 
T : A:635_A:638   β-turn 633-636; 635 &636 colored blue; β-turn 636-639, 637 & 638 blue. 
T : A:669_A:670   β-turn 668-671; 669 & 670 blue, other two are white. 
T : A:676_A:677   β-turn 675-678; last three residues part of helix, 675 is white. 
T : A:683_A:685   β-turn 682-685; 682 & 683 are the end of a helix, other two are blue. 
T : A:694_A:695   β-turn 693-696; last two residues are part of a helix, 694 is blue, 693 is white. 
T : A:728_A:728    728 is the first residue of an α-helix 
T : A:747_A:750   β-turn 748-751; 748-750 are blue, 751 is white. 
T : A:752_A:753   β-turn 751-754; 752 & 753 are blue, 754 is white. 
T : A:773_A:773    773 is the first residue in an α-helix 
T : A:777_A:777    777 is part of same α-helix as 773 
T : A:807_A:807    807 is part of an α-helix & a β-turn (805-808) nested in the helix. 
T : A:822_A:825   5-turns at 820-825 & 821-826; 822-824 are part of helix, 825 is blue, 826 is white. 

=== Identify turns using resourses at RCSB ===
When the structure is large and complex as it is in the complete chain A glycogen phosphorylase, you may not be able to see the small high lighted turn after clicking on the annotation bar. The turn or any other secondary structure, when it is selected on the annotation bar, is centered in the Jmol applet so that when the structure is zoomed the turn will become enlarged and visible in the center of the applet. If you want to view the turn in isolation, in the Jmol menu click on 'Select' and choose 'Display Selected Only'. This menu item works as a toogle switch so the complete structure can be turned back on. Run 'calculate hbonds structure' in the lower box of the Jmol console displays all the hbonds involved in the secondary structures. Use end note to open glycogen phosphorylase chain A.<ref>[http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3NP7&params.showJmol=true Open glycogen phosphorylase, chain A (3np7.pdb) with Jmol applet displayed]</ref>
</StructureSection>

== References ==
<references />

Secondary structure

2012-06-21T01:06:53Z

Karl Oberholser:

<applet load='1dtg' size='400' frame='true' align='right' caption='' scene='Secondary_structure/1dtg_ss/6'/>__NOTOC__

Secondary structure of a protein refers to the three-dimensional structure of local segments of a protein. Each type of secondary structure has segments that have a repeating conformational pattern which is produced by a repeating pattern of values for the [[Psi and Phi Angles|phi and psi torsional angles]]. For this reason, on a [[Ramachandran Plots|Ramachandran plot]], the values for phi and psi are located at a particular area of the plot for each secondary structure.

There are three common secondary structures - helices, β-pleated sheets and turns, and there are several variations of each one of them.
*'''Helices'''. Alpha helix, pi helix and 310 helix are the three types of helices with the alpha helix being the most important. The characteristics of these three helices are given at [[Helices in Proteins]]. [[Jmol]] colors them alpha helix, 310 helix and pi helix as shown in [[Helices in Proteins]].

*'''Strands'''. The strands making up the sheets can be parallel or antiparallel and the pleats in the sheet can be twisted as well as being parallel. These structural differences and other characteristics of β-sheets can be seen at [[Sheets in Proteins]].

*'''Turns'''. β-turn and γ-turn are the two types of turns. β-turns are composed of four amino acids and can have several difference conformations. γ-turns are made up of only three amino acids and are therefore a much tighter turn. More detail and illustrations of these turns are at [[Turns in Proteins]].

The structure of a human transferrin n-lobe mutant (PDB code [[1dtg]]) shows the presence of alpha helices, 310 helices, beta-sheets, and beta-turns. Another example, <scene name='Secondary_structure/Gly_phosphyl/3'>domain 2 of glycogen phosphorylase</scene> (PDB code [[1abb]]), contains a pi helix in addition to the above structures.
{{Clear}}
<table width='410' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Secondary Structures of Sample Proteins'''<scene name='Secondary_structure/1dtg_ss/6'> (Initial scene)</scene></center></td></tr></table>
{{Clear}}
==How Jmol Determines Secondary Structure==
===From PDB files===
[[PDB files]] usually contain HELIX and SHEET records, in their headers. (Many PDB files used to contain TURN records, but in revision 3.2 of the [[PDB files|PDB data format]], TURN records were abolished.) These represent the authors' determinations, and when present, [[Jmol]] obeys them (see [[Help:Color Keys#Secondary Structure|secondary structure colors]]). Secondary structure assignments are somewhat arbitrary. Proteins are not rigid (unlike PDB files!), and phi/psi angles may change from instant to instant. For example, there may be an alpha helix with a small kink in the middle. Objective software may determine that this represents two alpha helices, while the authors may specify it as a single helix.

Jmol's standard color scheme for secondary structure (see [[Help:Color_Keys]]):
<center>

{{Template:ColorKey_Helix}},
{{Template:ColorKey_Strand}},
{{Template:ColorKey_Turn}}.

</center>

===Jmol's objective calculation===
When the PDB file lacks HELIX and SHEET records, Jmol will determine secondary structure using objective criteria. Optionally, using Jmol [[Scene_authoring_tools#Using_Jmol.27s_Command_Language|command language]], you can re-determine secondary structure objectively, overriding the authors' specifications in the PDB file. '[[Calculate structure]]' is the Jmol command which does this re-determination. The complete script required to display the ''Secondary Structure'' color scheme and hydrogen bonds (hbonds) contained in the secondary structures is 'select protein; calculate structure; cartoon; color structure; calculate hbonds structure'. At the present time 'calculate hbonds structure' messes up the post-processing by Proteopedia, and any scene whose script contains this command is not displayed. The above scenes which colors the helices, sheets and turns without displaying the hbonds were constructed using only 'select protein; calculate structure; cartoon; color structure'. If 'calculate hbonds strucutre' is run through the Jmol console as described below, the hbonds in these three types of structures will be displayed.
<blockquote>
Hbonds in secondary structures can be displayed by clicking on the ''Jmol frank'' which opens the ''main menu'', clicking on ''Console'', in the bottom console box entering the commands: select protein; calculate hbonds structure
and then clicking ''Run''.</blockquote>

<blockquote>
If a Proteopedia page does not contain the more detailed ''Secondary Structure'' information, it can be displayed by running the script:
select protein; calculate structure; cartoon; color structure; calculate hbonds structure in the Jmol console as described above.
</blockquote>

More detail on how calculate structure determines helices, strands and turns is at [[Calculate structure]].

== See Also ==
* [http://en.wikipedia.org/wiki/Secondary_structure Wikipedia's page on secondary structure].
* [[Calculate structure]]
* [[Membrane proteins]]
* [[Help:Color Keys]]

==External Resources==
* [http://bioinf.cs.ucl.ac.uk/psipred/ The PSIPRED Protein Structure Prediction Server] has a highly accurate method for protein secondary structure prediction for proteins where there is no empirically-determined 3D structure.

Secondary structure

2012-06-21T01:01:57Z

Karl Oberholser:

<applet load='1dtg' size='400' frame='true' align='right' caption='' scene='Secondary_structure/1dtg_ss/6'/>__NOTOC__

Secondary structure of a protein refers to the three-dimensional structure of local segments of a protein. Each type of secondary structure has segments that have a repeating conformational pattern which is produced by a repeating pattern of values for the [[Psi and Phi Angles|phi and psi torsional angles]]. For this reason, on a [[Ramachandran Plots|Ramachandran plot]], the values for phi and psi are located at a particular area of the plot for each secondary structure.

There are three common secondary structures - helices, β-pleated sheets and turns, and there are several variations of each one of them.
*'''Helices'''. Alpha helix, pi helix and 310 helix are the three types of helices with the alpha helix being the most important. The characteristics of these three helices are given at [[Helices in Proteins]]. [[Jmol]] colors them alpha helix, 310 helix and pi helix as shown in [[Helices in Proteins]].

*'''Strands'''. The strands making up the sheets can be parallel or antiparallel and the pleats in the sheet can be twisted as well as being parallel. These structural differences and other characteristics of β-sheets can be seen at [[Sheets in Proteins]].

*'''Turns'''. β-turn and γ-turn are the two types of turns. β-turns are composed of four amino acids and can have several difference conformations. γ-turns are made up of only three amino acids and are therefore a much tighter turn. More detail and illustrations of these turns are at [[Turns in Proteins]].

The structure of a human transferrin n-lobe mutant (PDB code [[1dtg]]) shows the presence of alpha helices, 310 helices, beta-sheets, and beta-turns. Another example, <scene name='Secondary_structure/Gly_phosphyl/3'>domain 2 of glycogen phosphorylase</scene> (PDB code [[1abb]]), contains a pi helix in addition to the above structures.
{{Clear}}
<table width='410' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Secondary Structures of Sample Proteins'''<scene name='Secondary_structure/1dtg_ss/6'> (Initial scene)</scene></center></td></tr></table>
{{Clear}}
==How Jmol Determines Secondary Structure==
===From PDB files===
[[PDB files]] usually contain HELIX and SHEET records, in their headers. (Many PDB files used to contain TURN records, but in revision 3.2 of the [[PDB files|PDB data format]], TURN records were abolished.) These represent the authors' determinations, and when present, [[Jmol]] obeys them (see [[Help:Color Keys#Secondary Structure|secondary structure colors]]). Secondary structure assignments are somewhat arbitrary. Proteins are not rigid (unlike PDB files!), and phi/psi angles may change from instant to instant. For example, there may be an alpha helix with a small kink in the middle. Objective software may determine that this represents two alpha helices, while the authors may specify it as a single helix.

Jmol's standard color scheme for secondary structure (see [[Help:Color_Keys]]):
<center>

{{Template:ColorKey_Helix}},
{{Template:ColorKey_Strand}},
{{Template:ColorKey_Turn}}.

</center>

===Jmol's objective calculation===
When the PDB file lacks HELIX and SHEET records, Jmol will determine secondary structure using objective criteria. Optionally, using Jmol [[Scene_authoring_tools#Using_Jmol.27s_Command_Language|command language]], you can re-determine secondary structure objectively, overriding the authors' specifications in the PDB file. '[[Calculate structure]]' is the Jmol command which does this re-determination. The complete script required to display the ''Secondary Structure'' color scheme and hydrogen bonds (hbonds) contained in the secondary structures is 'select protein; calculate structure; cartoon; color structure; calculate hbonds structure'. At the present time 'calculate hbonds structure' messes up the post-processing by Proteopedia, and any scene whose script contains this command is not displayed. The above scenes which colors the helices, sheets and turns without displaying the hbonds were constructed using only 'select protein; calculate structure; cartoon; color structure'. If 'calculate hbonds strucutre' is run through the Jmol console as described below, the hbonds in these three types of structures will be displayed.
<blockquote>
Hbonds in secondary structures can be displayed by clicking on the ''Jmol frank'' which opens the ''main menu'', clicking on ''Console'', in the bottom console box entering the command: calculate hbonds structure
and then clicking ''Run''.</blockquote>
<blockquote>
If a Proteopedia page does not contain the more detailed ''Secondary Structure'' information, it can be displayed by running the script:
select protein; calculate structure; cartoon; color structure; calculate hbonds structure in the Jmol console as described above.
</blockquote>

More detail on how calculate structure determines helices, strands and turns is at [[Calculate structure]].

== See Also ==
* [http://en.wikipedia.org/wiki/Secondary_structure Wikipedia's page on secondary structure].
* [[Calculate structure]]
* [[Membrane proteins]]
* [[Help:Color Keys]]

==External Resources==
* [http://bioinf.cs.ucl.ac.uk/psipred/ The PSIPRED Protein Structure Prediction Server] has a highly accurate method for protein secondary structure prediction for proteins where there is no empirically-determined 3D structure.

Secondary structure

2012-06-21T00:43:39Z

Karl Oberholser:

<applet load='1dtg' size='400' frame='true' align='right' caption='' scene='Secondary_structure/1dtg_ss/6'/>__NOTOC__

Secondary structure of a protein refers to the three-dimensional structure of local segments of a protein. Each type of secondary structure has segments that have a repeating conformational pattern which is produced by a repeating pattern of values for the [[Psi and Phi Angles|phi and psi torsional angles]]. For this reason, on a [[Ramachandran Plots|Ramachandran plot]], the values for phi and psi are located at a particular area of the plot for each secondary structure.

There are three common secondary structures - helices, β-pleated sheets and turns, and there are several variations of each one of them.
*'''Helices'''. Alpha helix, pi helix and 310 helix are the three types of helices with the alpha helix being the most important. The characteristics of these three helices are given at [[Helices in Proteins]]. [[Jmol]] colors them alpha helix, 310 helix and pi helix as shown in [[Helices in Proteins]].

*'''Strands'''. The strands making up the sheets can be parallel or antiparallel and the pleats in the sheet can be twisted as well as being parallel. These structural differences and other characteristics of β-sheets can be seen at [[Sheets in Proteins]].

*'''Turns'''. β-turn and γ-turn are the two types of turns. β-turns are composed of four amino acids and can have several difference conformations. γ-turns are made up of only three amino acids and are therefore a much tighter turn. More detail and illustrations of these turns are at [[Turns in Proteins]].

The structure of a human transferrin n-lobe mutant (PDB code [[1dtg]]) shows the presence of alpha helix, 310 helix, beta-sheets, and beta-turns. Another example, <scene name='Secondary_structure/Gly_phosphyl/3'>domain 2 of glycogen phosphorylase</scene> (PDB code [[1abb]]), contains pi helix in addition to the above structures.
{{Clear}}
<table width='410' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Secondary Structures of Sample Proteins'''<scene name='Secondary_structure/1dtg_ss/6'> (Initial scene)</scene></center></td></tr></table>
{{Clear}}
==How Jmol Determines Secondary Structure==
===From PDB files===
[[PDB files]] usually contain HELIX and SHEET records, in their headers. (Many PDB files used to contain TURN records, but in revision 3.2 of the [[PDB files|PDB data format]], TURN records were abolished.) These represent the authors' determinations, and when present, [[Jmol]] obeys them (see [[Help:Color Keys#Secondary Structure|secondary structure colors]]). Secondary structure assignments are somewhat arbitrary. Proteins are not rigid (unlike PDB files!), and phi/psi angles may change from instant to instant. For example, there may be an alpha helix with a small kink in the middle. Objective software may determine that this represents two alpha helices, while the authors may specify it as a single helix.

Jmol's standard color scheme for secondary structure (see [[Help:Color_Keys]]):
<center>

{{Template:ColorKey_Helix}},
{{Template:ColorKey_Strand}},
{{Template:ColorKey_Turn}}.

</center>

===Jmol's objective calculation===
When the PDB file lacks HELIX and SHEET records, Jmol will determine secondary structure using objective criteria. Optionally, using Jmol [[Scene_authoring_tools#Using_Jmol.27s_Command_Language|command language]], you can re-determine secondary structure objectively, overriding the authors' specifications in the PDB file. '[[Calculate structure]]' is the Jmol command which does this re-determination. The complete script required to display the ''Secondary Structure'' color scheme and hydrogen bonds (hbonds) contained in the secondary structures is 'select protein; calculate structure; cartoon; color structure; calculate hbonds structure'. At the present time 'calculate hbonds structure' messes up the post-processing by Proteopedia, and any scene whose script contains this command is not displayed. The above scenes which colors the helices, sheets and turns without displaying the hbonds were constructed using only 'select protein; calculate structure; cartoon; color structure'. If 'calculate hbonds strucutre' is run through the Jmol console as described below, the hbonds in these three types of structures will be displayed.
<blockquote>
Hbonds in secondary structures can be displayed by clicking on the ''Jmol frank'' which opens the ''main menu'', clicking on ''Console'', in the bottom console box entering the command: calculate hbonds structure
and then clicking ''Run''.</blockquote>
<blockquote>
If a Proteopedia page does not contain the more detailed ''Secondary Structure'' information, it can be displayed by running the script:
select protein; calculate structure; cartoon; color structure; calculate hbonds structure in the Jmol console as described above.
</blockquote>

More detail on how calculate structure determines helices, strands and turns is at [[Calculate structure]].

== See Also ==
* [http://en.wikipedia.org/wiki/Secondary_structure Wikipedia's page on secondary structure].
* [[Calculate structure]]
* [[Membrane proteins]]
* [[Help:Color Keys]]

==External Resources==
* [http://bioinf.cs.ucl.ac.uk/psipred/ The PSIPRED Protein Structure Prediction Server] has a highly accurate method for protein secondary structure prediction for proteins where there is no empirically-determined 3D structure.

Secondary structure

2012-06-21T00:26:55Z

Karl Oberholser:

<applet load='1dtg' size='400' frame='true' align='right' caption='' scene='Secondary_structure/1dtg_ss/4'/>

Secondary structure of a protein refers to the three-dimensional structure of local segments of a protein. Each type of secondary structure has segments that have a repeating conformational pattern which is produced by a repeating pattern of values for the [[Psi and Phi Angles|phi and psi torsional angles]]. For this reason, on a [[Ramachandran Plots|Ramachandran plot]], the values for phi and psi are located at a particular area of the plot for each secondary structure.

There are three common secondary structures - helices, β-pleated sheets and turns, and there are several variations of each one of them.
*'''Helices'''. Alpha helix, pi helix and 310 helix are the three types of helices with the alpha helix being the most important. The characteristics of these three helices are given at [[Helices in Proteins]]. [[Jmol]] colors them alpha helix, 310 helix and pi helix as shown in [[Helices in Proteins]].

*'''Strands'''. The strands making up the sheets can be parallel or antiparallel and the pleats in the sheet can be twisted as well as being parallel. These structural differences and other characteristics of β-sheets can be seen at [[Sheets in Proteins]].

*'''Turns'''. β-turn and γ-turn are the two types of turns. β-turns are composed of four amino acids and can have several difference conformations. γ-turns are made up of only three amino acids and are therefore a much tighter turn. More detail and illustrations of these turns are at [[Turns in Proteins]].

The structure of a human transferrin n-lobe mutant (PDB code [[1dtg]]) shows the presence of alpha helix, 310 helix, beta-sheets, and beta-turns. Another example is <scene name='Secondary_structure/Gly_phosphyl/3'>domain 2 of glycogen phosphorylase</scene> (PDB code [[1abb]]).
{{Clear}}
<table width='410' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Secondary Structures of Sample Proteins'''<scene name='Secondary_structure/1dtg_ss/4'> (Initial scene)</scene></center></td></tr></table>

==How Jmol Determines Secondary Structure==
===From PDB files===
[[PDB files]] usually contain HELIX and SHEET records, in their headers. (Many PDB files used to contain TURN records, but in revision 3.2 of the [[PDB files|PDB data format]], TURN records were abolished.) These represent the authors' determinations, and when present, [[Jmol]] obeys them (see [[Help:Color Keys#Secondary Structure|secondary structure colors]]). Secondary structure assignments are somewhat arbitrary. Proteins are not rigid (unlike PDB files!), and phi/psi angles may change from instant to instant. For example, there may be an alpha helix with a small kink in the middle. Objective software may determine that this represents two alpha helices, while the authors may specify it as a single helix.

Jmol's standard color scheme for secondary structure (see [[Help:Color_Keys]]):
<center>

{{Template:ColorKey_Helix}},
{{Template:ColorKey_Strand}},
{{Template:ColorKey_Turn}}.

</center>

===Jmol's objective calculation===
When the PDB file lacks HELIX and SHEET records, Jmol will determine secondary structure using objective criteria. Optionally, using Jmol [[Scene_authoring_tools#Using_Jmol.27s_Command_Language|command language]], you can re-determine secondary structure objectively, overriding the authors' specifications in the PDB file. '[[Calculate structure]]' is the Jmol command which does this re-determination. The complete script required to display the ''Secondary Structure'' color scheme and hydrogen bonds (hbonds) contained in the secondary structures is 'select protein; calculate structure; cartoon; color structure; calculate hbonds structure'. At the present time 'calculate hbonds structure' messes up the post-processing by Proteopedia, and any scene whose script contains this command is not displayed. The above scenes which colors the helices, sheets and turns without displaying the hbonds were constructed using only 'select protein; calculate structure; cartoon; color structure'. If 'calculate hbonds strucutre' is run through the Jmol console as described below, the hbonds in these three types of structures will be displayed.
<blockquote>
Hbonds in secondary structures can be displayed by clicking on the ''Jmol frank'' which opens the ''main menu'', clicking on ''Console'', in the bottom console box entering the command: calculate hbonds structure
and then clicking ''Run''.</blockquote>
<blockquote>
If a Proteopedia page does not contain the more detailed ''Secondary Structure'' information, it can be displayed by running the script:
select protein; calculate structure; cartoon; color structure; calculate hbonds structure in the Jmol console as described above.
</blockquote>

More detail on how calculate structure determines helices, strands and turns is at [[Calculate structure]].

== See Also ==
* [http://en.wikipedia.org/wiki/Secondary_structure Wikipedia's page on secondary structure].
* [[Calculate structure]]
* [[Membrane proteins]]
* [[Help:Color Keys]]

==External Resources==
* [http://bioinf.cs.ucl.ac.uk/psipred/ The PSIPRED Protein Structure Prediction Server] has a highly accurate method for protein secondary structure prediction for proteins where there is no empirically-determined 3D structure.

Secondary structure

2012-06-21T00:22:34Z

Karl Oberholser:

<applet load='1dtg' size='400' frame='true' align='right' caption='' scene='Secondary_structure/1dtg_ss/4'/>

Secondary structure of a protein refers to the three-dimensional structure of local segments of a protein. Each type of secondary structure has segments that have a repeating conformational pattern which is produced by a repeating pattern of values for the [[Psi and Phi Angles|phi and psi torsional angles]]. For this reason, on a [[Ramachandran Plots|Ramachandran plot]], the values for phi and psi are located at a particular area of the plot for each secondary structure.

There are three common secondary structures - helices, β-pleated sheets and turns, and there are several variations of each one of them.
*'''Helices'''. Alpha helix, pi helix and 310 helix are the three types of helices with the alpha helix being the most important. The characteristics of these three helices are given at [[Helices in Proteins]]. [[Jmol]] colors them alpha helix, 310 helix and pi helix as shown in [[Helices in Proteins]].

*'''Strands'''. The strands making up the sheets can be parallel or antiparallel and the pleats in the sheet can be twisted as well as being parallel. These structural differences and other characteristics of β-sheets can be seen at [[Sheets in Proteins]].

*'''Turns'''. β-turn and γ-turn are the two types of turns. β-turns are composed of four amino acids and can have several difference conformations. γ-turns are made up of only three amino acids and are therefore a much tighter turn. More detail and illustrations of these turns are at [[Turns in Proteins]].

The structure of a human transferrin n-lobe mutant (PDB code [[1dtg]]) shows the presence of alpha helix, 310 helix, beta-sheets, and beta-turns. Another example is <scene name='Secondary_structure/Gly_phosphyl/3'>domain 2 of glycogen phosphorylase</scene> (PDB code [[1abb]]).
{{Clear}}
<table width='410' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Secondary Structures of Sample Proteins'''<scene name='Secondary_structure/1dtg_ss/4'> (Initial scene)</scene></center></td></tr></table>

==How Jmol Determines Secondary Structure==
===From PDB files===
[[PDB files]] usually contain HELIX and SHEET records, in their headers. (Many PDB files used to contain TURN records, but in revision 3.2 of the [[PDB files|PDB data format]], TURN records were abolished.) These represent the authors' determinations, and when present, [[Jmol]] obeys them (see [[Help:Color Keys#Secondary Structure|secondary structure colors]]). Secondary structure assignments are somewhat arbitrary. Proteins are not rigid (unlike PDB files!), and phi/psi angles may change from instant to instant. For example, there may be an alpha helix with a small kink in the middle. Objective software may determine that this represents two alpha helices, while the authors may specify it as a single helix.

Jmol's standard color scheme for secondary structure (see [[Help:Color_Keys]]):
<center>

{{Template:ColorKey_Helix}},
{{Template:ColorKey_Strand}},
{{Template:ColorKey_Turn}}.

</center>

===Jmol's objective calculation===
When the PDB file lacks HELIX and SHEET records, Jmol will determine secondary structure using objective criteria. Optionally, using Jmol [[Scene_authoring_tools#Using_Jmol.27s_Command_Language|command language]], you can re-determine secondary structure objectively, overriding the authors' specifications in the PDB file. '[[Calculate structure]]' is the Jmol command which does this re-determination. The complete script required to display the ''Secondary Structure'' color scheme and hydrogen bonds (hbonds) contained in the secondary structures is 'select protein; calculate structure; cartoon; color structure; calculate hbonds structure'. At the present time 'calculate hbonds structure' messes up the post-processing by Proteopedia, and any scene whose script contains this command is not displayed. The above scenes which colors the helices, sheets and turns without displaying the hbonds were constructed using only 'select protein; calculate structure; cartoon; color structure'. If 'calculate hbonds strucutre' is run through the Jmol console as described below, the hbonds in these three types of structures will be displayed.
<blockquote>
Hbonds in secondary structures can be displayed by clicking on the ''Jmol frank'' which opens the ''main menu'', clicking on ''Console'', in the bottom console box entering the command: calculate hbonds structure
and then clicking ''Run''.</blockquote>
<blockquote>
If a Proteopedia page does not contain the more detailed ''Secondary Structure'' information, it can be displayed by running the script:
select protein; calculate structure; cartoon; color structure; calculate hbonds structure in the Jmol console as described above.
</blockquote>

See [[Calculate structure]] for more details.
===Examples===
If the above series of commands are applied when the structure of a human transferrin n-lobe mutant is displayed, you will see that in additional to the sheets and the '''alpha helices''' being displayed the '''310 helices''' and different types of turns in blue are also shown. If the above series of commands are applied when the structure of glycogen phosphorylase (domain 2) is displayed above, all four chains will be initially displayed, but clicking the ''domain 2 of glycogen phosphorylase'' green link (above) will display only domain 2 of chain A. You will observe all three types of helices, and the turns will be colored blue. More detail on how calculate structure determines helices, strands and turns is at [[Calculate structure]].

== See Also ==
* [http://en.wikipedia.org/wiki/Secondary_structure Wikipedia's page on secondary structure].
* [[Calculate structure]]
* [[Membrane proteins]]
* [[Help:Color Keys]]

==External Resources==
* [http://bioinf.cs.ucl.ac.uk/psipred/ The PSIPRED Protein Structure Prediction Server] has a highly accurate method for protein secondary structure prediction for proteins where there is no empirically-determined 3D structure.