Proteopedia - User contributions [en]

File:Top 71 centerForBioMolecularModeling.jpg

2019-07-31T19:22:27Z

Mark Hoelzer: 3-D printed physical model of top71

== Summary ==
3-D printed physical model of top71
== Licensing ==
{{subst:Permission from license selector}}

File:SodiumChannel 2 centerForBiomolecularModeling.jpg

2019-07-31T19:21:26Z

Mark Hoelzer: 3-D printed physical model of sodiumChannel

== Summary ==
3-D printed physical model of sodiumChannel
== Licensing ==
{{subst:Permission from license selector}}

File:SodiumChannel 1 centerForBiomolecularModeling.jpg

2019-07-31T19:20:56Z

Mark Hoelzer: 3-D printed physical model of sodiumChannel

== Summary ==
3-D printed physical model of sodiumChannel
== Licensing ==
{{subst:Permission from license selector}}

File:SecondarStructure 2 centerForBiomolecularModeling.jpg

2019-07-31T19:20:24Z

Mark Hoelzer: 3-D printed physical model of secondaryStructure.

== Summary ==
3-D printed physical model of secondaryStructure.
== Licensing ==
{{subst:Permission from license selector}}

File:SecondarStructure 1 centerForBiomolecularModeling.jpg

2019-07-31T19:19:45Z

Mark Hoelzer: 3-D printed physical model of secondaryStructure.

== Summary ==
3-D printed physical model of secondaryStructure.
== Licensing ==
{{subst:Permission from license selector}}

File:ScorpionToxin 3 centerForBiomolecularModeling.jpg

2019-07-31T19:19:07Z

Mark Hoelzer: 3-D printed physical model of scorpionToxin.

== Summary ==
3-D printed physical model of scorpionToxin.
== Licensing ==
{{subst:Permission from license selector}}

File:ScorpionToxin 2 centerForBiomolecularModeling.jpg

2019-07-31T19:18:30Z

Mark Hoelzer: 3-D printed physical model of scorpionToxin.

== Summary ==
3-D printed physical model of scorpionToxin.
== Licensing ==
{{subst:Permission from license selector}}

File:ScorpionToxin 1 centerForBiomolecularModeling.jpg

2019-07-31T19:17:56Z

Mark Hoelzer: 3-D printed physical model of scorpionToxin.

== Summary ==
3-D printed physical model of scorpionToxin.
== Licensing ==
{{subst:Non-commercial from license selector}}

File:PotassiumChannel 2 centerForBiomolecularModeling.jpg

2019-07-31T19:17:19Z

Mark Hoelzer: 3-D printed physical model of potassiumChannel

== Summary ==
3-D printed physical model of potassiumChannel
== Licensing ==
{{subst:Permission from license selector}}

File:PotassiumChannel 1 centerForBiomolecularModeling.jpg

2019-07-31T19:16:44Z

Mark Hoelzer: 3-D printed physical model of potassiumChannel.

== Summary ==
3-D printed physical model of potassiumChannel.
== Licensing ==
{{subst:Permission from license selector}}

File:Integrin 1 centerForBiomolecularModeling.jpg

2019-07-31T19:16:04Z

Mark Hoelzer: 3-D printed physical model of integrin.

== Summary ==
3-D printed physical model of integrin.
== Licensing ==
{{subst:Permission from license selector}}

File:Insulin 4 centerForBiomolecularModeling.jpg

2019-07-31T19:15:31Z

Mark Hoelzer: 3-D printed physical model of insulin.

== Summary ==
3-D printed physical model of insulin.
== Licensing ==
{{subst:Permission from license selector}}

File:Insulin 3 centerForBiomolecularModeling.jpg

2019-07-31T19:14:55Z

Mark Hoelzer: 3-D printed physical model of insulin.

== Summary ==
3-D printed physical model of insulin.
== Licensing ==
{{subst:Permission from license selector}}

File:Insulin 2 centerForBiomolecularModeling.jpg

2019-07-31T19:14:13Z

Mark Hoelzer: 3-D printed physical model of insulin.

== Summary ==
3-D printed physical model of insulin.
== Licensing ==
{{subst:Permission from license selector}}

File:Insulin 1 centerForBiomolecularModeling.jpg

2019-07-31T19:13:33Z

Mark Hoelzer: 3-D printed physical model of insulin

== Summary ==
3-D printed physical model of insulin
== Licensing ==
{{subst:Permission from license selector}}

Hemagglutinin

2019-07-31T19:09:09Z

Mark Hoelzer:

<StructureSection load='' size='350' side='right' scene ='Hemagglutinin/Blackground2wre/1' caption='Structure of glycosylated viral hemagglutinin trimer complex with galactose ([[2wre]])'>
== Function ==
[[Hemagglutinin|Hemagglutinins]] (HA) are one of the two antigenic Glycoproteins inserted into the influenza virus' membrane. There are at least 16 different forms of HA antigens classified from H1 to H16. H1, H2, H3 are specific to human [[influenza]]. HAs have two main functions crucial for the [[Viral Infections|viral infection]] cycle:
1. On the target cell, HA binds the receptor on the cell membrane which is contains sialic acid <ref>Gottschalk A. Chemistry of virus receptors. The Viruses. 1959;3:51–61.</ref> allowing the virus/cell interaction.
2. HA induce the fusion between the host cell and the virus which can entry into the cytoplasm.
Because the HA are the major Antigens of the Virus, [[Antibody|Antibodies]] recognized them and for this reason HA often change. '''Hemagglutinin-neuraminidase''' (HN) is multifunctional. It possesses both the receptor recognition and neuraminidase activities<ref>PMID:21680512</ref>. For details see [[Mumps Virus Hemagglutinin Neuraminidase Protein]].

For discussion of influenza hemagglutinin see 
*[[Influenza hemagglutinin]] 
*[[Influenza]] 
*[[User:Michael Strong/H1N1/HA]] 
*[[User:Michael Strong/H1N1/HA/MSA]] for multiple sequence alignment.

==Hemagglutinin Structure==
HA is an <scene name='Hemagglutinin/Homotrimer/2'>homotrimer</scene> integral membrane glycoprotein. Each monomer is synthesized like a single polypeptide chain almost 550 amino acids. This precursor is then glycosilated and cleaved into two smaller polypeptides by removal of Arginine 329; at the same time, a conformational change occurs in the monomer.

The HA1 and HA2 subunits are covalently attached by a <scene name='SAndbox_159/Disulfide_bond/2'>disulfide bond</scene> from HA1 position 14 to HA2 position 467(*). These two chains form one monomer, and the noncovalentely association of three monomers forms one hemagglutinin molecule: (HA1+HA2)3. It is principally stabilized by packing of the alpha-helixes. All molecules are 135 Angström long.

The <scene name='SAndbox_159/Ha1/1'>HA1 subunit</scene> (328 amino acids) has a globular form outside the virus’ membrane: it is composed by an eight-stranded beta-sheet, associated with a little alpha-helix, separating the strands 3 and 4.
The amino acids of this alpha-helix, and some others around it, included in the beta-sheet, compose the binding site for the receptor’s sialic acid. Thus, for one molecule of hemagglutinin, there are three binding sites to the host cell’s receptor.

The <scene name='SAndbox_159/Ha2/2'>HA2 subunit</scene> (221 amino acids) has a hair spin structure composed by two antiparallel alpha-helixes. One of these belongs to the longest alpha-helixes in globular protein: it is 50 angstrom long. The hydrophobic N-terminus part of HA2, called fusion peptide, is close to a protease’s cleavage site: this protease is implied in the virus’ entry in the host cell.

HA1 and HA2 are bound each other by a disulfide bind. The three long alpha-helixes (of the three HA2) are coiled-coil to form a central region of 40 Angström, and thank to the hydrophobic amino acids and those which form salt bridges bound, we obtain a HA stabilized.<ref>PMID: 3304138</ref>

==2WRE==

To begin, this code corresponds to the structure of influenza H2 Avian Hemagglutinin from the “Asian Influenza” of 1957.<ref>PMID :19805083</ref> Human receptor.
- At the position 226, Avian Hemagglutinin has a Glutamine residue whereas the Human one has Leucine

- At the position 228, there is a Glycin for Avian HA whereas a Serine for Human HA.

These two mutations prevent the human H2 binding on the avian receptor whereas the human receptor can be bound by avian hemagglutinin that lacks the human specific mutation of H2 pandemic viruses.

There are three sites for sialic acid binding, which are at the membrane-distal tips of the identical monomers that form the HA trimer:

- The first one is the <scene name='SAndbox_159/Loop_220/2'>Loop 220</scene> composed by the residues from 225 to 228

- The second is called <scene name='SAndbox_159/Loop_130/1'>Loop 130</scene> and contains the residues 131 to 137

- the last is named 190-helix

[[Image:Avian.jpg|300px|thumb]]
{{Clear}}
The residues of these loops 130 and 220 have carbonyl oxygens and amide nitrogens of peptide bonds exposed with potential to interact with the receptor, which is composed by Gal-1 and Sia-2.
The avian H2 can bind the human receptor because of intramolecular Hydrogen bond network created by Gln 226 and by Asn 186.
Four amino acids compose <scene name='SAndbox_159/Receptor_binding_site/3'>the receptor binding site</scene>: Tyr 98, Ser 136, Trp 153(**), His 183, (which are identical in the all different HA)(*). This site forms a pocket on the distal end of the molecule. The binding structure is stabilized by other conserved which cannot interact with the receptor
<scene name='SAndbox_159/Amino_acids_in_the_stability/1'>(Cys 97, Pro 99, Cis139, Pro 147, Tyr 195, Arg 229).</scene>(*)
The Sia-1-Gal-2 glycosidic bond adopts a cis conformation. Extensive hydrogen bond direction are settled between avian and Gal-2 of the receptor: two water molecules (Wat-1 and Wat-2) have a significant role in mediating these interactions(see fig.1).
The site chain of Lys-222 and the main chain carbonyl at 225 are linked by Wat-1 to the 3'OH of Gal-2. Gln-226 and Asn 186 form hydrogen bonds with the hydroxyl groups of 4'C of Gal-2 and 9'C of Sia-1.<ref>Cell Binding protein in Avian Influenza; Jack Cerchiara,'06 and Brendan Holsberry, 07;http://biology.kenyon.edu/BMB/Chime2/2005/Cerchiara-Holsberry/FRAMES/start.htm</ref>

==Oligosaccharides==

Some <scene name='SAndbox_159/Asparagines/1'>Asparagines</scene> of HA1 (8, 22, 38, 81, 165, 285)(*) have oligosaccharides chains attached to them. The seventh oligasaccharide is linked to an Aspargine of HA2 (484). All of them are complex oligosaccharides and are on the lateral surfaces of the molecule, except for site and 165. No precise functions have been assigned to them, even if the oligosaccharide at 165 seems to allow the stabilisation of oligomeric contact between globular units at the top of the protein's structure.

==Antigenic variability==

Each Hemagglutinin monomer contains four antigenic sites called <scene name='SAndbox_159/Antigenic_site/1'>A,B,C and D sites</scene>. "A"(in red) site is a loop that protrudes 8 Angström distally from the surface of the target membrane. "B"(in green) site is composed by the external amino acids of one alpha helix and several amino acids of the receptor binding site which contains the sialic acid. "C"(in blue) site is a 60 Angström bulge from the distal extremity of HA. To finish, "D"(in mangenta) site is located in two beta-sheet of the jelly roll of HA1 globular extremity.

The substitutions of amino acids in these sites allow the influenza virus to escape from the immune system and to spread. Major changes in these antigenic regions can produce lethal influenza pandemics, like in 1957.

==How Influenza Escapes Vaccines==

Influenza hemagglutinin (''e.g.'' [[1hgf]]) is a glycoprotein on the surface of [http://en.wikipedia.org/wiki/Influenza_virus influenza virus] particles that enables them to attach to and infect host cells. [[Antibody|Antibodies]] that bind to hemagglutinin are a major defense mechanism that prevent infection. The RNA genome of influenza is characterized by a high mutation rate. Mutations on the surface of hemagglutinin tend to be protective for the virus. They tend to be retained because they tend to reduce the binding strength, and hence the host defensive capability, of antibodies that recognize the un-mutated hemagglutinin<ref name="skehel_review">PMID: 16925526</ref>. Influenza vaccines include hemagglutinins and they induce anti-hemagglutinin antibodies in vaccinated individuals. Often, however, by the time the vaccines can be designed, produced, and disseminated, mutant influenza viruses have arisen that can cause disease in vaccinated individuals<ref name="fluwikipedia">See [http://en.wikipedia.org/wiki/Influenza Influenza] in Wikipedia.</ref>.
If you '''show''' the '''Evolutionary Conservation''' of the structure on this page (using the blue bars below the molecule), you will see highly variable surface amino acids. These represent sites of mutations that have been retained in wild strains of influenza because they improve virus survival<ref name="skehel_review" />. (Added by [[User:Eric Martz|Eric Martz]]).

==Notes==
(*)These four amino-acids don't have the same numbering in the text and on the picture because there is a frame shift between the PDB and the Swissprot sequence numbering.

(**) The amino acid 153 lacks for the A monomer chain.

==3D structures of hemagglutinin==
[[Hemagglutinin 3D structures]]

==3D Printed Physical Models of Hemagglutinin==

Shown below are 3D printed physical models of Hemagglutinin. The model is shown as an alpha carbon backbone, with key sidechains and domains highlighted. It has been designed with precisely embedded magnets that allow the three chains to pull apart into individual pieces.

[[Image:hemagglutinin_1_centerForBiomolecularModeling.jpg | 450px]][[Image:hemagglutinin_2_centerForBiomolecularModeling.jpg | 450px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

</StructureSection>

==Additional Resources==
For additional information, see: [[Influenza]]
 

==References==
<references/>

[[Category: Topic Page]]

Influenza

2019-07-31T19:04:06Z

Mark Hoelzer:

[[Image:800px-H1N1_navbox.jpg|350px|right|thumb| Picture of the H1N1 Influenza Virus]]

[[Influenza]], commonly known as the Flu, is caused by RNA viruses of the family Orthomyxoviridae and takes the life of nearly 500,000 people per year. 

Articles in Proteopedia concerning [[Influenza]] include:
{{#tree:id=IndexByTopic|openlevels=1|
* [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
* H1N1 Sequence Analyses
** [[User:Michael_Strong/H1N1|H1N1 Swine Flu Sequence Analysis]]
** [[User:Michael_Strong/H1N1/MP1/MSA|H1N1 Swine Flu Multiple Sequence Alignment]]
** [[User:Michael Strong/H1N1/MP2/MSA|H1N1 Sequence Alignment of MP2 Protein]]
** [[User:Michael_Strong/H1N1/PB2|H1N1 Sequence Alignment of PB2 Protein]]
** [[User:Michael_Strong/H1N1/PB1|H1N1 Sequence Alignment of PB1 Protein]]
** [[User:Michael_Strong/H1N1/NS2/MSA|H1N1 Sequence Alignment of NS2 Protein]]
** [[User:Michael_Strong/H1N1/PA|H1N1 Sequence Alignment of PA Protein]]
** [[User:Michael_Strong/H1N1/HA|H1N1 Sequence Alignment of HA Protein]]
** [[User:Michael_Strong/H1N1/NP|H1N1 Sequence Alignment of NP Protein]]
** [[User:Michael_Strong/H1N1/NA|H1N1 Sequence Alignment of NA Protein]]
** [[User:Michael_Strong/H1N1/MP|H1N1 Sequence Alignment of MP Protein]]
** [[User:Michael_Strong/H1N1/NS|H1N1 Sequence Alignment of NS Protein]]
* [[Hemagglutinin]]
* [[Influenza hemagglutinin]]
* [[Molecular_Playground/Influenza_A_M2_transmembrane_domain|Influenza A M2 Transmembrane Domain]]
* [[Proton Channels]] w/ morph of the M2 proton channel of influenza.
* [[Molecular Playground/Tamiflu|Tamiflu Interaction]]
* [[Molecular Playground/Relenza|Relenza Interaction]]
}}
 

To view automatically seeded indices concerning [[Influenza]] See:
*[[:Category:Influenza|Influenza]]
*[[:Category:Influenza_a_virus|Influenza A Virus]]
*[[:Category:Influenza_protein|Influenza Proteins]]
*[[:Category:H1n1|H1N1]] 
 

To View FDA Approved Treatments for [[Influenza]] See: [[Pharmaceutical_Drugs#Treatments|Treatments]] 
To view other Proteopedia pages about diseases & drug targets, See: [[Pharmaceutical_Drug_Targets|Pharmaceutical Drug Targets]]

==3D Printed Physical Model of the Influenza Virus==

Shown below is a 3D printed physical model of the Influenza Virus. The membrane is yellow, the neuraminidase proteins are pink, the hemagglutinin proteins are purple, and the proton pump proteins are light blue. The model has been designed with an opening to allow the schematic addition or removing of genome segments.

[[Image:haVirus_1_centerForBiomolecularModeling.jpg | 750px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

Influenza

2019-07-31T19:03:42Z

Mark Hoelzer:

[[Image:800px-H1N1_navbox.jpg|350px|right|thumb| Picture of the H1N1 Influenza Virus]]

[[Influenza]], commonly known as the Flu, is caused by RNA viruses of the family Orthomyxoviridae and takes the life of nearly 500,000 people per year. 

Articles in Proteopedia concerning [[Influenza]] include:
{{#tree:id=IndexByTopic|openlevels=1|
* [[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
* H1N1 Sequence Analyses
** [[User:Michael_Strong/H1N1|H1N1 Swine Flu Sequence Analysis]]
** [[User:Michael_Strong/H1N1/MP1/MSA|H1N1 Swine Flu Multiple Sequence Alignment]]
** [[User:Michael Strong/H1N1/MP2/MSA|H1N1 Sequence Alignment of MP2 Protein]]
** [[User:Michael_Strong/H1N1/PB2|H1N1 Sequence Alignment of PB2 Protein]]
** [[User:Michael_Strong/H1N1/PB1|H1N1 Sequence Alignment of PB1 Protein]]
** [[User:Michael_Strong/H1N1/NS2/MSA|H1N1 Sequence Alignment of NS2 Protein]]
** [[User:Michael_Strong/H1N1/PA|H1N1 Sequence Alignment of PA Protein]]
** [[User:Michael_Strong/H1N1/HA|H1N1 Sequence Alignment of HA Protein]]
** [[User:Michael_Strong/H1N1/NP|H1N1 Sequence Alignment of NP Protein]]
** [[User:Michael_Strong/H1N1/NA|H1N1 Sequence Alignment of NA Protein]]
** [[User:Michael_Strong/H1N1/MP|H1N1 Sequence Alignment of MP Protein]]
** [[User:Michael_Strong/H1N1/NS|H1N1 Sequence Alignment of NS Protein]]
* [[Hemagglutinin]]
* [[Influenza hemagglutinin]]
* [[Molecular_Playground/Influenza_A_M2_transmembrane_domain|Influenza A M2 Transmembrane Domain]]
* [[Proton Channels]] w/ morph of the M2 proton channel of influenza.
* [[Molecular Playground/Tamiflu|Tamiflu Interaction]]
* [[Molecular Playground/Relenza|Relenza Interaction]]
}}
 

To view automatically seeded indices concerning [[Influenza]] See:
*[[:Category:Influenza|Influenza]]
*[[:Category:Influenza_a_virus|Influenza A Virus]]
*[[:Category:Influenza_protein|Influenza Proteins]]
*[[:Category:H1n1|H1N1]] 
 

To View FDA Approved Treatments for [[Influenza]] See: [[Pharmaceutical_Drugs#Treatments|Treatments]] 
To view other Proteopedia pages about diseases & drug targets, See: [[Pharmaceutical_Drug_Targets|Pharmaceutical Drug Targets]]

==3D Printed Physical Model of the Influenza Virus==

Shown below is a 3D printed physical model of the Influenza Virus. The membrane is yellow, the neuraminidase proteins are pink, the hemagglutinin proteins are purple and the proton pump proteins are light blue. The model has been designed with an opening to allow the schematic addition or removing of genome segments.

[[Image:haVirus_1_centerForBiomolecularModeling.jpg | 750px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

Fibrinogen

2019-07-31T19:01:25Z

Mark Hoelzer:

<StructureSection load='1n73' size='350' side='right' scene='41/410324/Cv/1' caption='Crystal structure of glycosylated fibrinogen fragment D. Subunit α (green and yellow), β (green and magenta), γ (pink and cyan) complex with the peptide ligand Gly-His-Arg-Pro-amide (red, wheat, blue, black) and Ca+2 ion (PDB code [[1n73]]) '>

== Function ==

'''Fibrinogen''' is a glycoprotein found in the blood that is converted into fibrin during blood coagulation. Fibrinogen is cleaved by another protein, [[thrombin]], exposing knobs A and B to form fibrin. <ref>PMID:16689770</ref> The fibrin forms clots to prevent excessive bleeding from wounds sustained. Clotting factors, like factor XIII, are often linked to fibrin. <ref>PMID:18673233</ref>

==3D Printed Physical Model of Fibrinogen==

Shown below is a 3D printed physical model of Fibrinogen. The structure is shown as an alpha carbon backbone colored by chain, with the three chains of each copy of fibrinogen colored yellow, blue and purple.

[[Image:fibrinogen1_centerForBioMolecularModeling.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

== Structural insights ==

Fibrinogen is composed of 2 copies each of 3 non-identical chains α, β, γ (<scene name='Fibrinogen/Fba/1'>Fba</scene>, <scene name='Fibrinogen/Fbb/1'>Fbb</scene>, <scene name='Fibrinogen/Fbg/1'>Fbg</scene>).
</StructureSection>

==3D Structure of Fibrinogen==

Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|

*Fibrinogen α+β+γ chains

**[[3hus]], [[3h32]], [[3e1i]], [[3bvh]], [[2hlo]], [[2hod]], [[2hpc]], [[2oyh]], [[2oyi]], [[2h43]], [[2ffd]], [[1re3]], [[1rf1]], [[1n86]], [[1ltj]] – hFba+hFbb+hFbg+peptide ligand – human 
**[[3ghg]], [[2q9i]], [[2z4e]] - hFba+hFbb+hFbg+knob A & B 
**[[2xnx]], [[2xny]] - hFba+hFbb+hFbg + M1 protein 
**[[2a45]] - hFba+hFbb+hFbg+thrombin+PPACK thrombin inhibitor 
**[[1re4]], [[1rf0]], [[1n8e]], [[1lt9]] - hFba+hFbb+hFbg 
**[[1jy3]], [[1deq]] – cFba+cFbb+cFbg – cow 
**[[1jy2]] - cFba+cFbb+cFbg proteolytic fragment 
**[[1n73]], [[1lwu]] - Fba+Fbb+Fbg+peptide ligand – Sea lamprey 
**[[1m1j]] - heFba+heFbb+heFbg+peptide ligand – hen 
**[[1ei3]] - heFba+heFbb+heFbg 

*Fibrinogen α chain

**[[1fzd]] – hFba EC domain 
**[[1bbr]] – hFba+cε-thrombin 
**[[2jor]] – cFba – NMR 
**[[2baf]] – cFba 

*Fibrinogen β chain

**[[1fzf]], [[1fzg]] – hFb fragment double-D +peptide ligand 
**[[1fze]], [[1fza]], [[1fzb]] – hFb fragment D 

*Fibrinogen γ chain

**[[2vr3]] – hFbg+SaClumping Factor A – ''Staphylococcus aureus'' 
**[[2vdo]], [[2vdp]], [[2vdq]], [[2vdr]] – hFbg+Integrin alpha IIB+Integrin beta-3+Monoclonal antibody heavy and light chains 
**[[2fib]], [[3fib]] - hFbg+peptide ligand 
**[[1fib]] – hFbg+Ca 
**[[1fic]], [[1fid]] – hFbg 
**[[3fib]] – hFbg C terminal 
**[[1dug]] – Fbg C-terminal/glutathione S-transferase – ''Schistosoma japonicum'' 
**[[2hwl]] – hFbg peptide+prothrombin 
**[[2y7l]] – hFbg + agglutinin-like protein 
}}
==References==
<references />

[[Category:Topic Page]]

Cystic fibrosis transmembrane conductance regulator (CFTR)

2019-07-31T18:59:58Z

Mark Hoelzer:

==Cystic fibrosis transmembrane conductance regulator (CFTR)==
<StructureSection load='5UAK' size='340' side='right' caption='Cystic Fibrosis Transmembrane Conductance regulator' scene=''>
The '''CFTR''' is a chloride channel, and is regulated by PKA phosphorylation, cAMP levels, and ATP/ADP ratios. Mutations in the CFTR cause the disease cystic fibrosis.

One feature of the CFTR is a Walker motif, which is found in ATP binding proteins.It is also known as a P (or phosphate binding) loop.

==3D Printed Physical Model of the CFTR protein==

Shown below are 3D printed physical models of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The backbone model on the left is colored by region, with the transmembrane domain white and the atp-binding and regulatory domains colored red. The backbone model on the right is colored by regional repeat, with the first repeat blue, the second repeat green and the regulatory domain colored red. The models have been designed with embedded magnets to disassemble into the key regions of the structure.

[[Image:cftr1_centerForBioMolecularModeling.jpg|500px]]
[[Image:cftr2_centerForBioMolecularModeling.jpg|500px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

</StructureSection>
== References ==
<references/>

Electron Transport Chain

2019-07-31T18:58:18Z

Mark Hoelzer: New page: ==3D Printed Physical Model of the Respiration Electron Transport Chain== Shown below is a 3D printed physical model of the Respiration Electron Transport Chain. Complex I is colored red,...

==3D Printed Physical Model of the Respiration Electron Transport Chain==

Shown below is a 3D printed physical model of the Respiration Electron Transport Chain. Complex I is colored red, complex II is purple, complex III is green, complex IV is blue and the atp synthetase protein is colored orange, yellow and red.

[[Image:atpSynthase_1_centerForBiomolecularModeling.jpg | 750px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Anthrax Toxin Protein

2019-07-31T18:52:32Z

Mark Hoelzer:

==3D Printed Physical Models of the Anthrax Toxin Protein==

Shown below are 3D printed physical models of the Anthrax Toxin Protein, based on the structure [http://proteopedia.org/wiki/index.php/1acc 1acc.pdb]. The full heptamer model is shown in spacefill format and is colored by domain, with a single monomer shown in white. The alpha carbon backbone model is similarly colored by chain, with additional key sidechains included.

[[Image:anthrax_1_centerForBiomolecularModeling.jpg | 500px]]
[[Image:anthrax_2_centerForBiomolecularModeling.jpg | 500px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Anthrax Toxin Protein

2019-07-31T18:52:04Z

Mark Hoelzer: New page: ==3D Printed Physical Models of the Anthrax Toxin Protein== Shown below are 3D printed physical models of the Anthrax Toxin Protein, based on the structure [http://proteopedia.org/wiki/in...

==3D Printed Physical Models of the Anthrax Toxin Protein==

Shown below are 3D printed physical models of the Anthrax Toxin Protein, based on the structure [http://proteopedia.org/wiki/index.php/1acc 1acc.pdb]. The full septamer model is shown in spacefill format and is colored by domain, with a single monomer shown in white. The alpha carbon backbone model is similarly colored by chain, with additional key sidechains included.

[[Image:anthrax_1_centerForBiomolecularModeling.jpg | 500px]]
[[Image:anthrax_2_centerForBiomolecularModeling.jpg | 500px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Adeno-Associated Virus

2019-07-31T18:48:05Z

Mark Hoelzer: New page: ==3D Printed Physical Models of an Adeno-Associated Virus== Shown below are 3D printed physical models of the Adeno-Associated Virus, based on the structure [http://proteopedia.org/wiki/i...

==3D Printed Physical Models of an Adeno-Associated Virus==

Shown below are 3D printed physical models of the Adeno-Associated Virus, based on the structure [http://proteopedia.org/wiki/index.php/3ux1 3ux1.pdb]. The capsid is colored by radial distance from the center of the sphere. It has been designed with embedded magnets to dock to a display base.

[[Image:adenoAssociatedVirus_1_centerForBiomolecularModeling.jpg | 500px]]
[[Image:adenoAssociatedVirus_2_centerForBiomolecularModeling.jpg | 500px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

File:HivProtease 2 centerForBiomolecularModeling.jpg

2019-07-31T17:48:14Z

Mark Hoelzer: 3-D printed physical model of HivProtease

== Summary ==
3-D printed physical model of HivProtease
== Licensing ==
{{subst:Permission from license selector}}

File:HivProtease 1 centerForBiomolecularModeling.jpg

2019-07-31T17:47:22Z

Mark Hoelzer: 3-D printed physical model of HivProtease

== Summary ==
3-D printed physical model of HivProtease
== Licensing ==
{{subst:Permission from license selector}}

File:Hemolysin 2 centerForBiomolecularModeling.jpg

2019-07-31T17:46:39Z

Mark Hoelzer: 3-D printed physical model of hemolysin

== Summary ==
3-D printed physical model of hemolysin
== Licensing ==
{{subst:Permission from license selector}}

File:Hemolysin 1 centerForBiomolecularModeling.jpg

2019-07-31T17:46:06Z

Mark Hoelzer: 3-D printed physical model of hemolysin

== Summary ==
3-D printed physical model of hemolysin
== Licensing ==
{{subst:Permission from license selector}}

File:Hemagglutinin 2 centerForBiomolecularModeling.jpg

2019-07-31T17:45:12Z

Mark Hoelzer: 3-D printed physical model of hemagglutinin

== Summary ==
3-D printed physical model of hemagglutinin
== Licensing ==
{{subst:Permission from license selector}}

File:HaVirus 1 centerForBiomolecularModeling.jpg

2019-07-31T17:44:02Z

Mark Hoelzer: 3-D printed physical model of haVirus

== Summary ==
3-D printed physical model of haVirus
== Licensing ==
{{subst:Non-commercial from license selector}}

File:Glut 1 centerForBiomolecularModeling.jpg

2019-07-31T17:42:24Z

Mark Hoelzer: 3-D printed physical model of glut

== Summary ==
3-D printed physical model of glut
== Licensing ==
{{subst:Permission from license selector}}

File:Gfp 2 centerForBiomolecularModeling.jpg

2019-07-31T17:41:16Z

Mark Hoelzer: 3-D printed physical model of gfp.

== Summary ==
3-D printed physical model of gfp.
== Licensing ==
{{subst:Permission from license selector}}

File:Gfp 1 centerForBiomolecularModeling.jpg

2019-07-31T17:40:04Z

Mark Hoelzer: 3-D printed physical model of gfp.

== Summary ==
3-D printed physical model of gfp.
== Licensing ==
{{subst:Permission from license selector}}

File:Fibrinogen 1 centerForBiomolecularModeling.jpg

2019-07-31T17:39:28Z

Mark Hoelzer: 3-D printed physical model of fibrinogen.

== Summary ==
3-D printed physical model of fibrinogen.
== Licensing ==
{{subst:Permission from license selector}}

File:Cftr 2 centerForBiomolecularModeling.jpg

2019-07-31T17:38:46Z

Mark Hoelzer: 3-D printed physical model of cftr.

== Summary ==
3-D printed physical model of cftr.
== Licensing ==
{{subst:Permission from license selector}}

File:Cftr 1 centerForBiomolecularModeling.jpg

2019-07-31T17:38:06Z

Mark Hoelzer: 3-D printed physical model of cftr.

== Summary ==
3-D printed physical model of cftr.
== Licensing ==
{{subst:Permission from license selector}}

File:AtpSynthase 1 centerForBiomolecularModeling.jpg

2019-07-31T17:37:20Z

Mark Hoelzer: 3-D printed physical model of atpSynthase.

== Summary ==
3-D printed physical model of atpSynthase.
== Licensing ==
{{subst:Permission from license selector}}

File:Antibody 1 centerForBiomolecularModeling.jpg

2019-07-31T17:36:27Z

Mark Hoelzer: 3-D printed physical model of an antibody.

== Summary ==
3-D printed physical model of an antibody.
== Licensing ==
{{subst:Permission from license selector}}

File:Anthrax 2 centerForBiomolecularModeling.jpg

2019-07-31T17:35:38Z

Mark Hoelzer: 3-D printed physical model of anthrax.

== Summary ==
3-D printed physical model of anthrax.
== Licensing ==
{{subst:Permission from license selector}}

File:Anthrax 1 centerForBiomolecularModeling.jpg

2019-07-31T17:34:44Z

Mark Hoelzer: 3-D printed physical model of anthrax.

== Summary ==
3-D printed physical model of anthrax.
== Licensing ==
{{subst:Permission from license selector}}

File:AdenoAssociatedVirus 2 centerForBiomolecularModeling.jpg

2019-07-31T17:33:18Z

Mark Hoelzer: 3-D physical printed model of an adenoAssociatedVirus.

== Summary ==
3-D physical printed model of an adenoAssociatedVirus.
== Licensing ==
{{subst:Permission from license selector}}

File:AdenoAssociatedVirus 1 centerForBiomolecularModeling.jpg

2019-07-31T17:31:44Z

Mark Hoelzer: 3-D physical model of an adenoAssociatedVirus.

== Summary ==
3-D physical model of an adenoAssociatedVirus.
== Licensing ==
{{subst:Permission from license selector}}

User:Mark Hoelzer/Sandbox1

2019-07-30T21:34:47Z

Mark Hoelzer:

==3D Printed Physical Model of Hemagglutinin==

Shown below is a 3D printed physical model of Hemagglutinin

[[Image:Hemagglutinin_1_centerForBiomolecularModeling.jpg]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 100px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

File:Hemagglutinin 1 centerForBiomolecularModeling.jpg

2019-07-30T21:32:27Z

Mark Hoelzer: 3D printed model of Hemagglutinin

== Summary ==
3D printed model of Hemagglutinin
== Licensing ==
{{subst:Permission from license selector}}

Hemoglobin

2018-05-10T21:02:42Z

Mark Hoelzer:

<StructureSection load='1gzx' size='350' side='right' caption="Human Hemoglobin α chain (grey and pink) β chain (green and yellow) with bound O2 [[1gzx]]" scene="Hemoglobin/1gzx/2" >
== Function ==
'''Hemoglobin''' is an oxygen-transport protein. Hemoglobin is an [[allosteric protein]]. It is a tetramer composed of two types of subunits designated α and β, with stoichiometry <scene name='Hemoglobin/Alpha2beta2/7'>α2β2</scene>. The <scene name='Hemoglobin/Foursubunits/5'>four subunits</scene> of hemoglobin sit roughly at the corners of a tetrahedron, facing each other across a <scene name='Hemoglobin/Cavity/9'>cavity</scene> at the center of the molecule. Each of the subunits <scene name='Hemoglobin/Bbsubunitswithheme/5'>contains a heme</scene> prosthetic group. The <scene name='Hemoglobin/4heme/3'>heme molecules</scene> give hemoglobin its red color.

Each individual <scene name='Hemoglobin/Deoxyheme/8'>heme</scene> molecule contains one <scene name='Hemoglobin/Deoxyheme_fe/9'>Fe2+</scene> atom. In the lungs, where oxygen is abundant, an <scene name='Hemoglobin/Oxyheme_fe/7'>oxygen molecule</scene> binds to the ferrous iron atom of the heme molecule and is later released in tissues needing oxygen. The heme group binds oxygen while still attached to the <scene name='Hemoglobin/Oxysubunit/8'>hemoglobin monomer</scene>. The spacefill view of the hemoglobin polypeptide subunit with an oxygenated heme group shows how the <scene name='Hemoglobin/Oxysubunitsf/4'>oxygenated heme group is held</scene> within the polypeptide.

<scene name='Hemoglobin/Anchortrace/5'>Anchoring of the heme</scene> is facilitated by a histidine nitrogen that binds to the iron. A second histidine is near the bound oxygen. The "arms" (propanoate groups) of the heme are hydrophilic and face the surface of the protein while the hydrophobic portions of the heme are buried among the hydrophobic amino acids of the protein.

Perhaps the most well-known disease caused by a mutation in the hemoglobin protein is sickle-cell anemia. It results from a mutation of the sixth residue in the β hemoglobin monomer from <scene name='32/32/Hemoglobins_1hho/9'>glutamic acid to a valine</scene>. This hemoglobin variant is termed 'hemoglobin S' ([[2hbs]]). See also 
[[Ann Taylor/Hemoglobin]] 
[[Molecular Playground/Hb-Hp Complex]] 
[[Porphyrin]] 
[[Student Projects for UMass Chemistry 423 Spring 2012-8]] 
[[Hemoglobin (Hebrew)]].

==Hemoglobin subunit binding O2==
For hemoglobin, its function as an oxygen-carrier in the blood is fundamentally linked to the equilibrium between the two main states of its quaternary structure, the unliganded "deoxy" or "T state" versus the liganded "oxy" or "R state". The unliganded (deoxy) form is called the "T" (for "tense") state because it contains extra stabilizing interactions between the subunits. In the high-affinity R-state conformation the interactions which oppose oxygen binding and stabilize the tetramer are somewhat weaker or "relaxed". In some organisms this difference is so pronounced that their Hb molecules dissociate into dimers in the oxygenated form. Structural changes that occur during this transition can illuminate how such changes result in important functional properties, such as cooperativity of oxygen binding and allosteric control by pH and anions. Hemoglobin is definitely not a pure two-state system, but the T to R transition provides the major, first-level explanation of its function.

The hemoglobin molecule (or "Hb") is a tetramer of two α and two β chains, of 141 and 146 residues in human. They are different but homologous, with a "globin fold" structure similar to [[myoglobin]].



Here we see a single <scene name='Hemoglobin/3hhb_chaina_rainbow/4'>α chain</scene> of hemoglobin, starting with an overview of the subunit. The 6 major and 2 short α-helices that make up the structure of a Hb subunit (the "globin fold") are <scene name='Hemoglobin/3hhb_chaina_heliceslabeled/4'>labeled A through H</scene>, which is the traditional naming scheme. For example, the proximal histidine (the tightest protein Fe ligand) is often called <scene name='Hemoglobin/3hhb_chaina_hisf9/5'>His F9</scene>, since it is residue 9 on helix F (it is residue 87 in the human α chain). The helices form an approximately-cylindrical bundle, with the heme and its central Fe atom bound in a <scene name='Hemoglobin/3hhb_chaina_efpocket/4'>hydrophobic pocket between the E and F helices</scene>.

<scene name='32/32/Cv/2'>In the present animation scene</scene> the oxy (in pink) and deoxy (in deepskyblue) α1 heme groups were superimposed on each other, to give a local comparison at this site, a closeup around the heme O2-binding site. The heme is quite domed in the deepskyblue T-state (deoxy) form, with the 5-coordinate, high-spin Fe (orange ball) out of the plane. In the pink R-state form a CO molecule is bound at the right (C in green,O in red); the Fe, now 6-coordinate low-spin, has moved into the heme plane, which has flattenened. The proximal His (at left) connects the Fe to helices on the proximal side, making the Fe position sensitive to changes in the globin structure and vice versa. Remember that this scene shows a subunit in the all-unliganded versus the all-liganded states of Hb; when oxygen binds to just one subunit, then its internal structure undergoes some but not all of these changes, depending on conditions. <jmol><jmolButton>
<script>if (_animating); anim pause;set echo bottom left; color echo white; font echo 20 sansserif;echo Animation Paused; else; anim resume; set echo off;endif;</script>
<text>Toggle Animation</text>
</jmolButton></jmol>


O2 binds in the same place as CO, with similar effects on the structure; however, for O2 the outer atom is angled rather than straight. The equilibrium between free and bound O2 is very rapid, with on and off rates that are sensitive to protein conformation. Both CO and NO dissociate from the Fe atom very slowly, so that these gases act as respiratory poisons. The α and β chains differ somewhat in their rates and relative affinities for O2 and other ligands, by virtue of heme-pocket differences, but the differences between affinities in the R vs T quaternary states are much larger.

Both α and β chains of Hb resemble [[myoglobin]] (the single-chain O2-binder in muscle), both in overall tertiary structure and in using an Fe atom centered in a heme group as the site where oxygen is reversibly bound. The heme is surrounded by a hydrophobic pocket, which is necessary in order for it to bind oxygen reversibly without undergoing oxidation or other undesirable reactions.

The heme binding pocket contains mostly <scene name='32/32/Heme_binding_pocket_apo/1'>hydrophobic residues</scene>, shown in grey. They actually surround the binding site so thoroughly that O2 cannot get in or out without parts of the protein moving out of the way a bit, so that its dynamic properties are essential to have any O2 binding at all; this restrictive process also increases the specificity of ligand binding.

The shift between R and T state requires subunit interactions and does not occur in myoglobin, or in isolated α or β chain monomers. These monomers bind O2 quite tightly, which would work well for loading O2 in the lungs but would not allow unloading it for delivery to the tissues. Therefore, the central critical feature of hemoglobin function is how it achieves, uses, and allosterically controls cooperativity between the 4 binding sites in the tetramer to tune O2 binding for satisfying physiological needs.

Linkage of the heme Fe through the proximal His results in tertiary-structure changes that can then transmit their effects to other subunits in the tetrameric assemblage. This allows O2 binding in one subunit to indirectly affect the affinitiy of other subunits. Briefly, inside the α chains the R/T equilibrium is reflected in changes in Fe spin state and position as it moves in or out of the heme plane; the proximal His changes distance and angle relative to the heme; the F helix shifts; Tyr 140 moves and its H-bond to backbone weakens; and both the C-terminus of the chain and Arg 141 move significantly at the interface. These movements are animated at this [[User:Jaime_Prilusky/How_do_we_get_the_oxygen_we_breathe|page]]. Changes at the subunit interface (coupled with changes at the Fe, as we have seen) alter the equilibrium between the deoxy and oxy quaternary structures, and conversely a change of quaternary structure alters the balance between the two states inside a given subunit. Each O2 that binds increases the likelihood of switching the tetramer into the oxy state, and once it switches, the O2 affinity at all sites increases because the local structure changes have either already occurred or are easier to make.

Click here to show the α1 subunit, but centered for the whole tetramer.

==The Hb tetramer T -> R transition==

The central cavity, is wider in the deoxy state, forming phosphate sites; quaternary structure change as rigid rotations of α-β dimers; α1-β2 contact overview; "ratchet" vs "hinge" at the a1b2 interface; α1-α2 salt bridges; charged groups at the C-terminus of β2 which stabilize the deoxy form; and finally a summary overview. (from PDB files bio3HHB and bio1HCO)

Look down one of the approximate 2-fold axes, with α subunits at the top and β subunits at the bottom. Notice that the hemes are quite far apart, so that their interactions must be mediated by the protein.
For a view down the exact crystallographic 2-fold axis from the β1- β2 end, click here: The yellowtint crosses are phosphate sites present in deoxy but not oxy Hb. In oxy Hb, the β subunits move closer together, squeezing out phosphates (such as 2,3 DPG), and allowing the N- and C-termini to interact. DPG and other phosphates bind much more strongly to the deoxy quaternary structure; therefore they necessarily push the equilibrium toward deoxy Hb, and because of that they decrease O2 affinity. Such regulatory phosphate molecules are useful in the blood, because their concentrations can be controlled to shift the Hb O2-binding curve so that it is working across the steepest and most efficient part under conditions in the lungs and tissues. For instance, at high altitude the body makes more DPG, to unload O2 more effectively in the muscles.

Like the [[PFK]], to the first approximation the Hb molecule consists of two "dimers" (α1-β1 and α2-β2), which rotate relative to each other as rigid bodies in the R-T transition. The α1-β1 unit undergoes relatively little internal rearrangement, but its overall rotation with respect to the α2-β2 unit is considerable. The net rotation of the two dimers alters their interactions with one another, most notably at the allosteric effector site between β1 and β2 (PO4 binding) and at the important α1-β2 interface, where mutations have the largest effect on Hb allosteric properties. Although the symmetry is not exact, similar parts of the subunits contact each other: the C helix, and the "FG corner" between helices F and G.

Have a look at a closeup that emphasizes the ratchet contact between the C helix of α1 and the FG corner of β2; His 97 of the β2 FG corner makes a large jump against Thr 38 and Thr 41 of the α1 C helix. In a closeup of the hinge contact, the motions are mainly rotations without much shift, between the α1 FG corner and the β2 C helix. Labels help identify these parts. Since this is a complex motion orchestrated between the fit of two quite different sets of contacts in the two states, this interface is critical to making Hb allostery work, and mutations of residues in this interface have been found to be especially likely to influence cooperativity and allostery.

There are salt links between α1 and α2, which stabilize the deoxy form. Here’s an overview down the exact 2-fold axis between the subunits, showing that there are two equivalent sets of interactions, on either side of the twofold.

Salt links at the C-terminus of β2 stabilize the deoxy T form and make a large contribution to the pH dependence of Hb oxygen binding, known as the Bohr Effect. In the making and breaking of these interactions, His β 146 moves a great deal, disrupting the salt link (charged H-bond) to Asp β 94 that is formed in the T state. Since His titrates near physiological pH, this interaction is quite pH sensitive. At low pH, when more protons are present, the His ring N is more likely to be protonated and positive; this strengthens its H-bond with Asp 94, thus favoring the T state and decreasing O2 affinity. The pH effect, or Bohr Effect, can be considered as allosteric regulation by the binding of protons. It is important biologically, because it promotes oxygen unloading in the tissues where proton concentrations are elevated, for instance by the production of lactic acid in muscle.

==Truncated hemoglobins==


<scene name='Journal:JBIC:8/Trhb/1'>Truncated hemoglobins</scene>, also known as 2/2 hemoglobins, can be further classified into three different groups (I, II, and III). Genomic sequences of bacteria, cyanobacteria, and plants indicate that trHbs are rather common. Group I, Group II, and Group III trHbs have distinct phylogenetic trees and show different ligand-binding properties. The Group I trHb of the ciliated protozoan ''Tetrahymena pyriformis'' (''Tp'' trHb) was first discovered by Keilin and Ryley in 1953.

It is known that trHbs exist in ciliates of the Tetrahymena group, but trHb structure and function remain poorly understood. To investigate trHb function with respect to stability of bound oxygen and protein structure, we measured the oxygen binding kinetics of Tetrahymena pyriformis trHb, and determined the crystal structure of the protein.

The three-dimensional structure of an <scene name='Journal:JBIC:8/Trhb/2'>Fe(II)-O2 complex of Tp trHb</scene> was determined at 1.73 Å resolution ([[3aq9]]). <scene name='Journal:JBIC:8/Trhb/3'>Tyr25 (B10) and Gln46 (E7) were hydrogen-bonded to a heme-bound dioxygen molecule</scene>. Tyr25 donated a hydrogen bond to the terminal oxygen atom, whereas Gln46 hydrogen-bonded to the proximal oxygen atom. Furthermore, <scene name='Journal:JBIC:8/Trhb/4'>Tyr25 was hydrogen-bonded to the Gln46 and Gln50 (E11) residues</scene>.

The O2 association and dissociation rate constants of ''T. pyriformis'' trHb were 5.5 μM-1 s-1, and 0.18 s-1, respectively. The oxygen affinity was determined to be 33 nM. The autooxidation rate constant was 3.8 x 10-3 h-1. These values are similar to those of <scene name='Journal:JBIC:8/Hbn/3'>HbN from Mycobacterium tuberculosis</scene>. Mutations at <scene name='Journal:JBIC:8/As/2'>Tyr25</scene>, <scene name='Journal:JBIC:8/Ad/2'>Gln46</scene>, and <scene name='Journal:JBIC:8/Trhb/11'>Gln50</scene> increased the O2 dissociation and autooxidation rate constants, and partly disrupted the hydrogen-bonding network.

An <scene name='Journal:JBIC:8/Ag/4'>Fe(III)-H2O complex of Tp trHb was formed following reaction of the Fe(II)-O2 complex of Tp trHb</scene>, in a crystal state, with nitric oxide. This suggests that ''Tp'' trHb functions in nitric oxide detoxification.

== 3D structure of hemoglobin ==
==3D Printed Physical Model of Hemoglobin==

Shown below is a 3D printed physical model of Hemoglobin, based on the structure [http://proteopedia.org/wiki/index.php/1a3n 1a3n.pdb]. The two alpha-globin chains are colored light red, the two beta globin chains are colored dark red, and the four heme groups are colored yellow. It has been designed with precisely embedded magnets that allow the four chains to pull apart into individual pieces.

[[Image:Cbm_hemoglobin1.jpg|550px]]
[[Image:Cbm_hemoglobin2.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

==See Also==
*[[Tutorial:How do we get the oxygen we breathe]]
*[[Ann Taylor/Hemoglobin]]
*[[Molecular Playground/Hemoglobin-Haptoglobin Complex]]
*Hemoglobin structure tutorial at [http://molviz.org MolviZ.Org].

==References, for further information on Hemoglobin==
'''To the structures used here:'''
*Baldwin (1980) "The crystal structure of human carbonmonoxy haemoglobin at 2.7A resolution", J. Mol. Biol. 136: 103. ([[1hco]]) [http://www.ncbi.nlm.nih.gov/pubmed/7373648 PMID: 7373648]
*Fermi, Perutz, Shaanan, & Fourme (1984) "The crystal structure of human deoxy haemoglobin at 1.74A resolution", J. Mol. Biol. 175: 159. ([[3hhb]])
*Jotaro Igarashi, Kazuo Kobayashi and Ariki Matsuoka (2011) "A hydrogen-bonding network formed by the B10-E7-E11 residues of a truncated hemoglobin from Tetrahymena pyriformis is critical for stability of bound oxygen and nitric oxide detoxification", J. Biol. Inorg. Chem. 16(4):599-609 ([[3aq9]]) [http://www.ncbi.nlm.nih.gov/pubmed/21298303 PMID: 21298303]

'''General treatments of Hb allostery:'''
*Perutz (1970) "Stereochemistry of cooperative effects in haemoglobin", Nature 228: 726
*Baldwin & Chothia (1979) "Haemoglobin. The structural changes related to ligand binding and its allosteric mechanism", J. Mol. Biol. 129: 175. [http://www.nature.com/nature/journal/v228/n5273/abs/228726a0.html link]
*Dickerson & Geis (1983) "Hemoglobin: Structure, Function, and Pathology", Benjamin/Cummings Publ., Menlo Park, CA
*Perutz (1989) "Mechanisms of cooperativity and allosteric regulation in proteins", Quarterly Rev. of Biophys. 22: 139-236
*Ackers, Doyle, Myers, & Daugherty (1992) "Molecular code for cooperativity in hemoglobin", Science 255: 54
*Perutz, Fermi, Poyart, Pagnier, & Kister (1993) "A novel allosteric mechanism in haemoglobin: Structure of bovine deoxyhaemoglobin, absence of specific chloride binding sites, and origin of the chloride-linked Bohr Effect in bovine and human haemoglobin", J. Mol. Biol. 233: 536
'''Hb structures in other quaternary states or intermediates:'''
*Silva, Rogers, & Arnone (1992) "A third quaternary structure of human hemoglobin A at 1.7A resolution", J. Biol. Chem. 267: 17248
*Smith, Lattman, & Carter (1991) "The mutation β99 Asp-Tyr stabilizes Y - A new, composite quaternary state of human hemoglobin", Proteins: Struct., Funct., Genet. 10: 81
*Liddington, Derewenda, Dodson, Hubbard, & Dodson (1992) "High resolution crystal structures and comparisons of T state deoxyhaemoglobin and two liganded T-state haemoglobins: T(α-oxy)haemoglobin and T(met)Haemoglobin", J. Mol. Biol. 228: 551
'''More information on hemoglobin'''
*Perutz, M.F. (1978) Hemoglobin Structure and Respiratory Transport, Scientific American, volume 239, number 6.
*Squires, J.E. (2002) Artificial Blood, Science 295, 1002.
*Vichinsky, E. (2002) New therapies in sickle cell disease. Lancet 24, 629.

{{Clear}}

=='''Content Donators'''==
Currently (June 22, 2008) most all of the content of this page comes from three main sources of generously donated content. Their work has been imported into this page. In their order of appearance on the page:
# '''Content adapted with permission from Eric Martz's hemoglobin tutorial at http://molviz.org'''
# '''Content adapted with permission from David S. Goodsell and Shuchismita Dutta's Molecule of the Month on Hemoglobin http://mgl.scripps.edu/people/goodsell/pdb/pdb41/pdb41_1.html'''
# '''Content adapted with permission from Jane S. and David C. Richardson's http://kinemage.biochem.duke.edu/'''

[[he:hebrew_hemoglobin]]
[[Category:Topic Page]]

File:Anthrax-toxin.gif

2018-05-10T21:01:31Z

Mark Hoelzer:

==3D Printed Physical Model of the Anthrax Toxin Protein==

Shown below are 3D printed physical models of the Anthrax Toxin Protein, based on the structure [http://proteopedia.org/wiki/index.php/1acc 1acc.pdb]. The full septamer model is shown in spacefill format and is colored by domain, with a single monomer shown in white. The alpha carbon backbone model is similarly colored by chain, with additional key side chains included.

[[Image:anthrax1_centerForBioMolecularModeling.jpg|550px]]
[[Image:anthrax2_centerForBioMolecularModeling.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

== Summary ==
http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/images/anthrax-toxin.gif
== Licensing ==
{{subst:No license from license selector|Don't know}}

Antibody

2018-05-10T21:00:45Z

Mark Hoelzer:

<StructureSection load='1hzh' size='350' side='right' scene='' caption='Glycosylated human Igg with heavy chains (red and light red), light chains (aqua and green) (PDB code [[1hzh]])'>

'''Antibodies''', also known as '''Immunoglobulins''' (Ig) are gamma globulin proteins, primarily found in the blood of vertebrates. These [[glycoproteins]] serve as a critical component of the immune system when the host fails to activate alternative compliment pathways or phagocytic cells in response to invading microorganisms or other [http://en.wikipedia.org/wiki/Antigen antigens]. The incredible specificity with which immunoglobulins bind to an antigen is based upon structural complementarity between the antigen and antibody <scene name='Antibody/1hzh_heavy_chains/1'>heavy </scene>and <scene name='Antibody/1hzh_light_chains/1'>light chains </scene>. It is this specificity that has made <scene name='Antibody/1hzh_starting_scene/3'>antibodies</scene> a critical component in laboratory and medical research. See more in 
[[IgA]] 
[[IgG Branco]] 
[[Monoclonal Antibody]]. 
For Anti-HIV Fab see [[Human Fab PG16]] 
For Anti-VEGF Fab see [[Bevacizumab]] (Avastin) 
For Anti-factor IX Fab see [[Conformation-specific anti-Factor IX antibodies]] 
For Anti-vitamin Fab see [[MR1 Binds Vitamin Metabolites]] .

[[Image:230px-B cell activation2.png|270px|left|thumb| Production of Antibodies by Plasma Cells]]
{{Clear}}
__TOC__
==Cellular Basis of Antibody Production==
When a foreign antigen binds to a B-lymphocyte ([http://en.wikipedia.org/wiki/B_cell B-cell]), it activates the B-cell, and upon stimulation by [http://en.wikipedia.org/wiki/Helper_t_cell helper T-cells], undergoes clonal proliferation and B-cell maturation into antibody forming [http://en.wikipedia.org/wiki/Plasma_cells plasma cells]. Each plasma cell is programmed to make an antibody of a single specificity, which it releases into the blood. <ref name="Roit"> Roit, I. M. Roit's Essential Immunology. Oxford: Blackwell Science Ltd., 1997.</ref> Once in the blood, antibodies aid [http://en.wikipedia.org/wiki/Humoral_immune_system the humoral immune system] in three predominant ways: They coat foreign pathogens preventing them from entering healthy cells or disrupting antigen function; they coat pathogens, stimulating their removal via [http://en.wikipedia.org/wiki/Opsonization opsonization] by [http://en.wikipedia.org/wiki/Phagocytes phagocytes]; and they trigger destruction of pathogens by stimulating the [http://en.wikipedia.org/wiki/Complement_system complement pathway] or by [http://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity Antibody Dependent Cell-mediated Cytotoxicity], among other immune responses. <ref>PMID:8476565</ref> <ref>PMID:16234578</ref> All of these functions rely heavily on accurate antigen binding and communication with other immune effector cells. The amazing specificity antibodies operate with is made possible by the physical structure of the antibody, which appears simplistic, but contains several levels of additional complexity.

==Structure of the Immunoglobulin==
<scene name='Antibody/1igt_starting_scene/3'>Refined Structure of an Intact IgG2a Monoclonal Antibody</scene> ([[1igt]]).

The basic functional unit of an antibody is an immunoglobulin monomer, but antibodies secreted from plasma cells are typically dimeric with occasional higher order structures. Typical secreted antibodies have a basic four-peptide structure of two identical <scene name='Antibody/1igt_heavy_chains/1'>heavy chains </scene>and two identical <scene name='Antibody/1igt_light_chains/1'>light chains</scene> joined together by interchain <scene name='Antibody/1igt_disulfide_bonds/2'>disulfide bonds</scene>, forming a “Y” shaped molecule. The disulfide bonds are positioned within a flexible region called the <scene name='Antibody/1igt_hinge_region/1'>hinge region</scene>, which seperates the lobes of the antibody from one another and provides ample flexibility to bind antigens effectively. <ref name="Roit" /> Each domain (2 heavy and 2 light) contain between 70-110 amino acids and are classified into different categories according to size and function. <ref>PMID:10545762</ref> Both domains, heavy and light, contain variable and constant regions that are crucial to antibody function. <ref>PMID:107164</ref>

===Heavy Chain===
There are five types of immunoglobulin heavy chains, in mammals, α, δ, ε, γ, and μ, and give rise to the five unique classes or isotypes of antibodies, IgA, IgD, IgE, IgG, and IgM, which differ in size and composition. Each <scene name='Antibody/1igt_heavy_chains_ribbon/1'>heavy chain </scene>has a <scene name='Antibody/1igt_startconstant_region/1'>constant region </scene> and <scene name='Antibody/1igt_start_heavy_variable/1'>variable region</scene>. The constant region is identical in all antibodies of the same isotype, but differ in antibodies of different isotypes; i.e. all IgA have the same sequence in their heavy chain constant region, but these constant regions differ between IgA and IgD, etc. <ref>PMID:15040582</ref> The α, δ, and γ heavy chains have a constant region composed of <scene name='Antibody/1igt_heavy_3_chains/1'>three tandem immunoglobulin domains</scene> while heavy chains ε and μ contain four. The variable region of the heavy chain in antibodies is different for all antibodies created by different B-cells. <ref>PMID:107164</ref>

[[Image:New Antibody2.JPG|450px|left|thumb| Typical Structure of an Antibody]]

===Light Chain===
Every antibody contains two <scene name='Antibody/1igt_light_chains_ribbon/1'>light chains </scene>that are identical to each other. There are two types of immunoglobulin light chains in mammals, labeled lambda and kappa, with only one represented in each antibody. Each light chain has one <scene name='Antibody/1igt_light_chains_constnat_reg/1'>constant domain </scene>followed by one <scene name='Antibody/1igt_light_chain_variable/1'>variable domain</scene>, with a total length of about 215 amino acids. <ref name="Roit" />

=== The Regions: Fab, Fv, CDR, and Fc.===
The immunoglobulin can be broken down into regions, each serving a different purpose:

====Variable Regions====
The <scene name='Antibody/1igt_fab_region/1'>Fab region </scene>(Fragment, Antigen Binding region) is composed of one constant and one variable domain from each heavy and light chain of the antibody. It is the part of the antibody that gives it its famous “Y” shape.<ref>PMID:9048542</ref> Held within the Fab region is the variable domain, also known as the Fv region.<ref>PMID:4569769</ref> Within the Fv region lie <scene name='Antibody/1igt_start_variable_loops/1'>“hypervariable regions,”</scene> positioned at one end of the variable domain where they form parts of the Beta-turn loops and are clustered close to each other in space. The clustering of the hypervariable loops at the tips of the variable regions where the antigen-binding site is located makes them perfect candidates for antigen recognition. <ref name="Roit" />The sequence heterogeneity of the three heavy and three light chain hypervariable loops creates significant antigen specificity diversity through variations in the binding surface nature and shape. Each hypervariable region can be viewed as an independent structure contributing to the complementarity of the biding site and antigen and is often referred to as a complementarity determining region (CDR). <ref>PMID:107164</ref>

====Constant Regions====
The remaining part of the antibody, namely the <scene name='Antibody/1igt_fc/2'>Fc region</scene>, does not play a role in binding the antigen, but rather is responsible for modulating the immune systems response to the formation of an antibody-antigen complex. The Fragment Crystallizable (Fc) region is composed of two heavy chain constant regions that are isotype specific. <ref>PMID:15040582</ref> Antibodies are glycoproteins because of <scene name='Antibody/1igt_glycosylation/1'>glycosylation </scene>at conserved positions in their Fc regions. This glycosylation is a critical component determing the rate of antibody clearance form the body.<ref>PMID:9032990</ref> Once an antibody binds to an antigen, the Fc region binds to Fc receptors, among other proteins, to mediate a host of different physiological responses ranging from oposonization, to degranulation of mast cells, to the release of cytokines and cytotoxic molecules, etc. resulting in the destruction of the pathogen. <ref>PMID:9052877</ref> Depending on the class of antibody, as dictated by the identity of the Fc region, the antibody half-life and distribution throughout the body varies. Further, since Fc receptors are antibody isotype specific, the type of immune response is dependent on the type of Fc region on the immunoglobulin, allowing for different immune responses to the same pathogen if necessary.<ref>PMID:11244038</ref> See table for brief characterization of Immunoglobulin isotypes:

{| class="wikitable" border="1" width="70%" style="text-align:center"
|-
! colspan="2" align="center"| Immunoglobulin Classes and Function
|-
! Class
! Function and Oligomeric State<ref name="Roit" />
|-
! IgG
| Dimeric - The most abundant Ig in the extravascular fluids. Neutralizes toxins and combats microorganisms by activating the compliment system and facilitating the binding of phagocytic cells.
|-
! [[IgA]]
| Dimeric - Is the major Ig in seromucous secretions, where it serves to defend the external body surfaces.
|-
! IgM
| Pentameric – It is an intravascular antibody and is produced very early in the immune response. Due to it high oligomeric state, it is extremely effective as a bacterial agglutinator and mediator of complement-dependent cytolysis, making it a powerful first-line defense against bacterial pathogens.
|-
! IgD
| Dimeric - It is present on the lymphocyte and functions together with IgM as the antigen receptor on naïve B-cells.
|-
! IgE
| It binds to mast cells and upon contact with antigen, leads to local recruitment of antimicrobial agents via degranulation of the mast cell and release of inflammatory mediators. IgE is important for certain kinds of parasitic infections and is responsible for the symptoms of [http://en.wikipedia.org/wiki/Atopy atopic allergies] like eczema and asthma.
|}

A model of the IgG molecule is present in the figure which indicates the spatial disposition and interaction of the domains in IgG. As Dr. Ivan Roitt writes in Essential Immunolgy, “To enable the Fab arms to have the freedom to move and twist so that they can align their hypervariable regions with the antigenic sites on large immobile carriers, and to permit the Fc structures to adjust spatially in order to trigger their effector functions, it is desirable for IgG to have a high degree of flexibility. And it has just that. Structural analysis shows that the Fab can ‘elbow-bend’ at its V-C junction and twist about the hinge, which itself can more properly be described as a loose thether, allowing the Fab and the Fc to drift relative to each other with remarkable suppleness. It could be said that movements like that make it a very sexy molecule!” <ref name="Roit" />

[[Image:VDJ recombination.png|400px|left|thumb| Image of V(D)J Recombination]]
{{Clear}}
<scene name='Antibody/Rituxan_starting_scene/1'>Crystal structure of Rituximab Fab in complex with an epitope peptide</scene> ([[2osl]]).

== Antibody Diversity ==
Considering the nearly infinite number of possible antigens that can invade the body, the immune system had to develop a method for accurately targeting each one of these compounds, ranging from small molecules, to stray proteins, to viruses capable of infecting cells. The antibody was the immune systems response to this problem. It has been estimated that humans generate about 10^10 different antigens, each capable of binding a unique epitope of an antigen. Since antibodies are proteins, and proteins are controlled by the genes from which they are transcribed, a clever system of gene shuffling and manipulations developed to enable the immune system to create a huge repertoire of antibodies from a limited number of genes. <ref>PMID:8612345</ref> The variable region of each immunoglobulin chain is encoded in several pieces known as gene segments. For heavy chains, these segments are called the variable (V), diversity (D), and joining (J) segments. (Only V and J exist for light chains) 50 V segments, 25 D segments, and 6 J segments exist and are randomly arranged and rearranged in the genome in a process called [http://en.wikipedia.org/wiki/VDJ_recombination V(D)J recombination]. Each B-cell is programmed to produce antibodies of a single V(D)J recombination order.

Additional diversity is created by the proteins RAG-1 and RAG-2 which introduce the double stranded breaks between V, D, and J segments to allow recombination. At this stage, nucleotides can either be deleted or inserted between adjoining segments before being ligated together. <ref name="Roit" /> This dramatically increases antibody diversity. Further diversity is created during B-cell proliferation when the variable chains undergo a high rate of point mutations in a process called [http://en.wikipedia.org/wiki/Somatic_hypermutation somatic hypermutation], creating daughter cells of the original B-cell that are slightly different. The antibodies which bind the antigen with the highest affinity are selected for in a process called [http://en.wikipedia.org/wiki/Affinity_maturation affinity maturation]. <ref>PMID:11869898</ref><ref>PMID:17337763</ref> Isotype switching is also possible after activation of the B-cell by a mechanism called “class switch recombination” allowing different immunological responses to the same antigen bound by the same variable regions.<ref>PMID:12884279</ref> Through this clever system, tens of billions of different glycoprotein antibodies can be created from less than 100 genes, allowing antibodies to bind <scene name='Antibody/Rituxan_binding_site/1'>structurally complimentary antigens</scene> with exquisite precision. The discovery of antobdy diversity generation won Susumu Tonegawa the [http://nobelprize.org/nobel_prizes/medicine/laureates/1987/press.html Nobel Prize in Medicine in 1987].

[[Image:FluorescentCells.jpg|300px|right|thumb| Direct Immuno fluorescence Antibody labeling]]
{{Clear}}
==Antibody Applications==
Detection of particular antibodies is very common in medical diagnostic testing. Numerous biochemical assays exist to detect whether antibodies for specific antigens are present in the blood or other bodily fluids such as antibodies against [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] or [http://en.wikipedia.org/wiki/HIV HIV], etc. Another common medical test involving antibodies is blood type detection in which an individual’s blood is screened against anti-A and anti-B antibodies to determine the identity of that individual’s [http://en.wikipedia.org/wiki/Blood_type blood antigen type]. <ref>PMID:13477267</ref>

Antibodies are also extremely powerful tools in the laboratory setting where they are commonly used in [http://en.wikipedia.org/wiki/Western_blot Western Blot] to detect specific proteins in a sample <ref>PMID:6266278</ref>; [http://en.wikipedia.org/wiki/Flow_cytometry flow cytometry], to differentiate cell types by their protein expression profiles; [http://en.wikipedia.org/wiki/Immunoprecipitation immunoprecipitation], to separate proteins from other compounds in a [http://en.wikipedia.org/wiki/Lysate lysate] and for cellular labeling. Numerous other examples exist. <ref>PMID:15353569</ref>

The last two decades have seen a dramatic increase in antibody based technologies both for the lab and medicine thanks to the invention of the monoclonal antiboy, a discovery that won Niels K. Jerne, Georges J.F. Köhler, César Milstein the [http://nobelprize.org/nobel_prizes/medicine/laureates/1984/press.html Nobel Prize in Medicine in 1984]. See: [[Monoclonal Antibody]] for additional information.
</StructureSection>
__NOTOC__

==3D Printed Physical Model of an Anitbody==

Shown below is a 3D printed physical model of an Antibody. The protein is displayed as an alpha carbon backbone, with the heavy chains colored white, the light chains colored red, and the glycan colored blue.
[[Image:antibody1_centerForBioMolecularModeling.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

==References==
<references />

==Additional Pages==
* [[IgA]]
* [[Epitopes]]
* [[Major Histocompatibility Complex Class I]]
* [[Monoclonal Antibody]]

==See Also==
* [[Variable Lymphocyte Receptors]]
*Antibody at [[High school teachers' resources]], where you will find tutorials on antibody structure.
*[http://en.wikipedia.org/wiki/Antibodies Antibodies] at Wikipedia.

[[Category:Topic Page]]

Cystic fibrosis transmembrane conductance regulator (CFTR)

2018-05-10T20:52:36Z

Mark Hoelzer:

==Cystic fibrosis transmembrane conductance regulator (CFTR)==
<StructureSection load='5UAK' size='340' side='right' caption='Cystic Fibrosis Transmembrane Conductance regulator' scene=''>
The CFTR is a chloride channel, and is regulated by PKA phosphorylation, cAMP levels, and ATP/ADP ratios. Mutations in the CFTR cause the disease cystic fibrosis.

One feature of the CFTR is a Walker motif, which is found in ATP binding proteins.It is also known as a P (or phosphate binding) loop.

This is a default text for your page '''Cystic fibrosis transmembrane conductance regulator (CFTR)'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

==3D Printed Physical Model of the CFTR protein==

Shown below are 3D printed physical models of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The backbone model on the left is colored by region, with the transmembrane domain white and the atp-binding and regulatory domains colored red. The backbone model on the right is colored by regional repeat, with the first repeat blue, the second repeat green and the regulatory domain colored red. The models have been designed with embedded magnets to disassemble into the key regions of the structure.
[[Image:cftr1_centerForBioMolecularModeling.jpg|550px]]
[[Image:cftr2_centerForBioMolecularModeling.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

</StructureSection>
== References ==
<references/>

Fibrinogen

2018-05-10T20:47:25Z

Mark Hoelzer:

<StructureSection load='1n73' size='350' side='right' scene='41/410324/Cv/1' caption='Crystal structure of glycosylated fibrinogen fragment D. Subunit α (green and yellow), β (green and magenta), γ (pink and cyan) complex with the peptide ligand Gly-His-Arg-Pro-amide (red, wheat, blue, black) and Ca+2 ion (PDB code [[1n73]]) '>

== Function ==

'''Fibrinogen''' is a glycoprotein found in the blood that is converted into fibrin during blood coagulation. Fibrinogen is cleaved by another protein, [[thrombin]], exposing knobs A and B to form fibrin. <ref>PMID:16689770</ref> The fibrin forms clots to prevent excessive bleeding from wounds sustained. Clotting factors, like factor XIII, are often linked to fibrin. <ref>PMID:18673233</ref>

==3D Printed Physical Model of Fibrinogen==

Shown below is a 3D printed physical model of Fibrinogen. The structure is shown as an alpha carbon backbone colored by chain, with the three chains of each copy of fibrinogen colored yellow, blue and purple.
[[Image:fibrinogen1_centerForBioMolecularModeling.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

== Structural insights ==

Fibrinogen is composed of 2 copies each of 3 non-identical chains α, β, γ (<scene name='Fibrinogen/Fba/1'>Fba</scene>, <scene name='Fibrinogen/Fbb/1'>Fbb</scene>, <scene name='Fibrinogen/Fbg/1'>Fbg</scene>).
</StructureSection>

==3D Structure of Fibrinogen==

Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|

*Fibrinogen α+β+γ chains

**[[3hus]], [[3h32]], [[3e1i]], [[3bvh]], [[2hlo]], [[2hod]], [[2hpc]], [[2oyh]], [[2oyi]], [[2h43]], [[2ffd]], [[1re3]], [[1rf1]], [[1n86]], [[1ltj]] – hFba+hFbb+hFbg+peptide ligand – human 
**[[3ghg]], [[2q9i]], [[2z4e]] - hFba+hFbb+hFbg+knob A & B 
**[[2xnx]], [[2xny]] - hFba+hFbb+hFbg + M1 protein 
**[[2a45]] - hFba+hFbb+hFbg+thrombin+PPACK thrombin inhibitor 
**[[1re4]], [[1rf0]], [[1n8e]], [[1lt9]] - hFba+hFbb+hFbg 
**[[1jy3]], [[1deq]] – cFba+cFbb+cFbg – cow 
**[[1jy2]] - cFba+cFbb+cFbg proteolytic fragment 
**[[1n73]], [[1lwu]] - Fba+Fbb+Fbg+peptide ligand – Sea lamprey 
**[[1m1j]] - heFba+heFbb+heFbg+peptide ligand – hen 
**[[1ei3]] - heFba+heFbb+heFbg 

*Fibrinogen α chain

**[[1fzd]] – hFba EC domain 
**[[1bbr]] – hFba+cε-thrombin 
**[[2jor]] – cFba – NMR 
**[[2baf]] – cFba 

*Fibrinogen β chain

**[[1fzf]], [[1fzg]] – hFb fragment double-D +peptide ligand 
**[[1fze]], [[1fza]], [[1fzb]] – hFb fragment D 

*Fibrinogen γ chain

**[[2vr3]] – hFbg+SaClumping Factor A – ''Staphylococcus aureus'' 
**[[2vdo]], [[2vdp]], [[2vdq]], [[2vdr]] – hFbg+Integrin alpha IIB+Integrin beta-3+Monoclonal antibody heavy and light chains 
**[[2fib]], [[3fib]] - hFbg+peptide ligand 
**[[1fib]] – hFbg+Ca 
**[[1fic]], [[1fid]] – hFbg 
**[[3fib]] – hFbg C terminal 
**[[1dug]] – Fbg C-terminal/glutathione S-transferase – ''Schistosoma japonicum'' 
**[[2hwl]] – hFbg peptide+prothrombin 
**[[2y7l]] – hFbg + agglutinin-like protein 
}}
==References==
<references />

[[Category:Topic Page]]

Glucose transport protein

2018-05-10T20:43:37Z

Mark Hoelzer:

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Glucose transport protein'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

==3D Printed Physical Model of Glucose Transport Protein (GLUT)==

Shown below are 3D printed physical models of the Glucose Transport Protein (GLUT). The backbone model on the left is colored by repeat regions, with the first half red and the second half blue. The spacefill model on the right is colored by atom type, with carbon gray, oxygen red, nitrogen blue and sulfur yellow.

[[Image:glut1_centerForBioMolecularModeling.jpg|550px]]

====The MSOE Center for BioMolecular Modeling====

[[Image:CbmUniversityLogo.jpg | left | 150px]]

The [http://cbm.msoe.edu MSOE Center for BioMolecular Modeling] uses 3D printing technology to create physical models of protein and molecular structures, making the invisible molecular world more tangible and comprehensible. To view more protein structure models, visit our [http://cbm.msoe.edu/educationalmedia/modelgallery/ Model Gallery].

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>