Tropomyosin: Difference between revisions

Line 1:

<references/><references/>{{STRUCTURE_1c1g|PDB=1c1g|SCENE=}}

[[Image:Tropomyosin Dimer-2.png | thumb | left| 300x180px | alt text | '''Tropomyosin:''' Coiled-Coil Dimer, which is composed of two alpha helices [http://www.pdb.org/pdb/explore/explore.do?structureId=1C1G (1C1G)] ]][[Image:B Lehman1.jpg | thumb | 300 x 430px | left | alt text | '''Tropomyosin''' (seen in yello and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure). (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/~~people/faculty~~/~~lehman~~/ Website]) ]]'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap (along the major grove of actin, see down & left). The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament. Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end. The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin). A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.

[[Image:Tropomyosin Dimer-2.png | thumb | left| 300x180px | alt text | '''Tropomyosin:''' Coiled-Coil Dimer, which is composed of two alpha helices [http://www.pdb.org/pdb/explore/explore.do?structureId=1C1G (1C1G)] ]][[Image:B Lehman1.jpg | thumb | 300 x 430px | left | alt text | '''Tropomyosin''' (seen in yello and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap along the major grove of actin (see down & left)<ref name="Gunning">Tropomyosins. I. Gunning, Peter, 1950- II. Series.[DNLM: 1. Tropomyosin. W1 AD559 v.644 2008 / WE 500 T856 2008]</ref>. The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament<ref name="Gunning"/>. Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end<ref name="Frye">PMID:20465283</ref>. The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin)<ref name="Gunning"/><ref name="Whitby">PMID:10651038</ref>. A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.

Its role in muscle mechanics has been well established as it is a major regulatory component of the contractile apparatus, but its role in non-muscle systems is becoming evermore clear. In mammals, there are at least 40 known isoforms, which are generated by alternative splicing of multiple genes. These isoforms in non-muscle systems contribute to actin's stability by increasing filament rigidity and protecting the filament from actin severing proteins, like [[gelsolin]] or [http://en.wikipedia.org/wiki/Cofilin cofilin]. The different isoforms also aid in recruitment of various proteins, including myosin (a family of molecular motors). The reason for tropomyosin's diversity is not well known, but it is thought to exist to function at different developmental stages in some species as well as function in specific cells of higher multicellular organisms.

Its role in muscle mechanics has been well established as it is a major regulatory component of the contractile apparatus, but its role in non-muscle systems is becoming evermore clear. In mammals, there are at least 40 known isoforms, which are generated by alternative splicing of multiple genes<ref name="Gunning"/><ref name="Frye"/>. These isoforms in non-muscle systems contribute to actin's stability by increasing filament rigidity and protecting the filament from actin severing proteins, like [[gelsolin]] or [http://en.wikipedia.org/wiki/Cofilin cofilin]. The different isoforms also aid in recruitment of various proteins, including myosin (a family of molecular motors)<ref name="Clayton"/><ref name="Stark"/>. The reason for tropomyosin's diversity is not well known, but it is thought to exist to function at different developmental stages in some species as well as function in specific cells of higher multicellular organisms<ref name="Gunning"/>.

Line 13:

#'''Superfamily:''' tropomyosin

#'''Family:''' pig [[http://www.pdb.org/pdb/explore/explore.do?structureId=1C1G 1c1g]]

<Structure load='1c1g' size='400' frame='true' align='left' caption='Tropomyosin Dimer: Click on Green Links (right) to see hydrophobic and ionic interactions between the two alpha helices' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'/> [[Image:Helical Wheel Respresentation of Tropomyosin.jpg | thumb | right | 333x200px | alt text | '''Helical Wheel Diagram Representation of Tropopomyosin:''' The coiled-coil dimer is stabilized by hydrophobic and ionic interactions (red=hydrophobic, blue=polar & green=charged).]] Categorization of tropomyosin's <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'>coiled-coil</scene> describes a unique pattern of amino acids within the primary structure of the alpha helices that comprise the dimer interface. The unique amino acid pattern, found within all coiled-coil proteins, is a heptad repeat, which follows a similar pattern to: '''H-P-P-H-C-P-C''', where H is hydrophobic, P is polar and C is charged. This heptad repeat forms a right handed alpha helical secondary structure (see right for alpha helix secondary structure). This alpha helix is special in that it forms a hydrophobic strip along one side, which will interface with an adjacent alpha helix that also contains the heptad repeat and hydrophobic strip. These strips aid in the dimerization of tropomyosin and is important in the characteristic coiled-coil domain.

<Structure load='1c1g' size='400' frame='true' align='left' caption='Tropomyosin Dimer: Click on Green Links (right) to see hydrophobic and ionic interactions between the two alpha helices' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'/> [[Image:Helical Wheel Respresentation of Tropomyosin.jpg | thumb | right | 333x200px | alt text | '''Helical Wheel Diagram Representation of Tropopomyosin:''' The coiled-coil dimer is stabilized by hydrophobic and ionic interactions (red=hydrophobic, blue=polar & green=charged)Image Reconstructed from <ref name="Gunning"/>.]] Categorization of tropomyosin's <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'>coiled-coil</scene> describes a unique pattern of amino acids within the primary structure of the alpha helices that comprise the dimer interface<ref name="Gunning"/>. The unique amino acid pattern, found within all coiled-coil proteins, is a heptad repeat, which follows a similar pattern to: '''H-P-P-H-C-P-C''', where H is hydrophobic, P is polar and C is charged<ref name="Gunning"/><ref name="Whitby"/>. This heptad repeat forms a right-handed alpha helical secondary structure (see right for alpha helix secondary structure)<ref name="Gunning"/>. This alpha helix is special in that it forms a hydrophobic strip along one side, which will interface with an adjacent alpha helix that also contains the heptad repeat and hydrophobic strip. These strips aid in the dimerization of tropomyosin and is important in the characteristic coiled-coil domain.

This coiled-coil domain is represented as a helical wheel diagram (see right), whereby the four amino acids (two from each alpha chain) that are adjacent to each other contribute to a <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_hydrophobic_aa/4'>hydrophobic interaction</scene>, represented in red, while the four amino acids (two from each alpha chain) flanking the hydrophobic core provide an <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_ionic_interaction/2'>ionic interaction</scene>, or salt-bridge represented as green. Both the hydrophobic and ionic interactions contribute to the stability of the dimer.

This coiled-coil domain is represented as a helical wheel diagram (see right), whereby the four amino acids (two from each alpha chain) that are adjacent to each other contribute to a <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_hydrophobic_aa/4'>hydrophobic interaction</scene>, represented in red, while the four amino acids (two from each alpha chain) flanking the hydrophobic core provide an <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_ionic_interaction/2'>ionic interaction</scene>, or salt-bridge represented as green. Both the hydrophobic and ionic interactions contribute to the stability of the dimer<ref name="Gunning"/><ref name="Whitby"/>.

The amino acids from each alpha chain interact with each other uniquely in that side chains of the helices interfacing will pack together in a knobs in holes arrangement. This is accomplished by the ridges of one helix fitting between the grooves (between amino acids) of the adjacent helix. This packing allows for the two alpha helices to wrap tightly around each other in a left handed supercoil conformation further stabilizing the tropomyosin dimer.

The amino acids from each alpha chain interact with each other uniquely in that side chains of the helices interfacing will pack together in a knobs in holes arrangement<ref name="Gunning"/>. This is accomplished by the ridges of one helix fitting between the grooves (between amino acids) of the adjacent helix. This packing allows for the two alpha helices to wrap tightly around each other in a left handed supercoil conformation further stabilizing the tropomyosin dimer<ref name="Gunning"/>.

Tropomyosin, as mentioned above, will form a long polymer along the length of actin in a head-to-tail overlap. <Structure load='3mtu' size='400' frame='true' align='right' caption='Tropomyosin end-to-end overlap region [http://www.rcsb.org/pdb/explore/explore.do?structureId=3MTU (3MTU)]' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'/>This <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'>overlap region</scene> occurs as the amino acids from the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_c_d/1'>N-terminus</scene> of one dimer overlaps with the amino acids of the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b/3'>C-terminus</scene> of another dimer. There are several <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b_e_f/1'>intermolecular contacts</scene> in the overlap region, which consist of ionic, hydrophobic and non-polar interactions. Interestingly, the most variation seen among tropomyosin isoforms is in the overlap region, which will affect polymer formation along the actin filament.

Tropomyosin, as mentioned above, will form a long polymer along the length of actin in a head-to-tail overlap<ref name="Frye"/>. <Structure load='3mtu' size='400' frame='true' align='right' caption='Tropomyosin end-to-end overlap region [http://www.rcsb.org/pdb/explore/explore.do?structureId=3MTU (3MTU)]' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'/>This <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'>overlap region</scene> occurs as the amino acids from the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_c_d/1'>N-terminus</scene> of one dimer overlaps with the amino acids of the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b/3'>C-terminus</scene> of another dimer. There are several <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b_e_f/1'>intermolecular contacts</scene> in the overlap region, which consist of ionic, hydrophobic and non-polar interactions<ref name="Frye"/>. Interestingly, the most variation seen among tropomyosin isoforms is in the overlap region, which will affect polymer formation along the actin filament<ref name="Frye"/>.

== Post-Translational Modifications ==

=== Post-Translational Modifications ===

There are two types of post-translational modifications to tropomyosin: acetylation and phosphorylation.

== Tropomyosin in Muscle and Non-Muscle Systems==

Muscle tissue is comprised of many muscle fibers or cells. Those muscle fibers consist of myofibrils that contain a series of contractile units called sarcomeres. Within this unit contains thick filaments, comprised mainly of [[myosin]], and thin filaments, which contains [[actin]], tropomyosin and [[troponin]]. Tropomyosin in striated muscle systems (skeletal and cardiac) acts to inhibit the myosin cross-bridges from binding to the myosin binding site on thin filaments, this tropomyosin state is in the "Blocked" position. When the muscle is stimulated, there is a rise in intracellular calcium stemming from a cascade of cellular processes. As the calcium is bathing the sarcomere, it will bind to the troponin complex, which is bound to both actin and tropomyosin. The troponin will displace the tropomyosin from a "Blocked" to a "Closed" position. This transition allows the myosin head to interact weakly with the myosin binding site. The tropomyosin is displaced to its final position, "Open" state, along actin filament as myosin binds to its site. These three tropomyosin states along the filament is referred to as the three state model. As the intracellular calcium concentration falls, the troponin no longer is able to displace tropomyosin and it will transition back to the "Blocked" state.

Muscle tissue is comprised of many muscle fibers or cells. Those muscle fibers consist of myofibrils that contain a series of contractile units called sarcomeres. Within this unit contains thick filaments, comprised mainly of [[myosin]], and thin filaments, which contains [[actin]], tropomyosin and [[troponin]]. Tropomyosin in striated muscle systems (skeletal and cardiac) acts to inhibit the myosin cross-bridges from binding to the myosin binding site on thin filaments, this tropomyosin state is in the "Blocked" position<ref name="Lehman">PMID:19341744</ref>. When the muscle is stimulated, there is a rise in intracellular calcium stemming from a cascade of cellular processes. As the calcium is bathing the sarcomere, it will bind to the troponin complex, which is bound to both actin and tropomyosin<ref name="Tyska">PMID:11810692</ref>. The troponin will displace the tropomyosin from a "Blocked" to a "Closed" position<ref name="Lehman"/>. This transition allows the myosin head to interact weakly with the myosin binding site. The tropomyosin is displaced to its final position, "Open" state, along actin filament as myosin binds to its site<ref name="Lehman"/>. These three tropomyosin states along the filament is referred to as the three state model<ref name="Lehman"/>. As the intracellular calcium concentration falls, the troponin no longer is able to displace tropomyosin and it will transition back to the "Blocked" state<ref name="Lehman"/>.

Tropomyosin: Difference between revisions

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@@ Line 1: / Line 1: @@
 <references/><references/>{{STRUCTURE_1c1g|PDB=1c1g|SCENE=}}
-[[Image:Tropomyosin Dimer-2.png | thumb | left| 300x180px | alt text | '''Tropomyosin:''' Coiled-Coil Dimer, which is composed of two alpha helices [http://www.pdb.org/pdb/explore/explore.do?structureId=1C1G (1C1G)] ]][[Image:B Lehman1.jpg | thumb | 300 x 430px | left | alt text | '''Tropomyosin''' (seen in yello and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure). (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/people/faculty/lehman/ Website]) ]]'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap (along the major grove of actin, see down & left).  The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament.  Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end.  The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin).  A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.
+[[Image:Tropomyosin Dimer-2.png | thumb | left| 300x180px | alt text | '''Tropomyosin:''' Coiled-Coil Dimer, which is composed of two alpha helices [http://www.pdb.org/pdb/explore/explore.do?structureId=1C1G (1C1G)] ]][[Image:B Lehman1.jpg | thumb | 300 x 430px | left | alt text | '''Tropomyosin''' (seen in yello and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap along the major grove of actin (see down & left)<ref name="Gunning">Tropomyosins. I. Gunning, Peter, 1950- II. Series.[DNLM: 1. Tropomyosin. W1 AD559 v.644 2008 / WE 500 T856 2008]</ref>.  The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament<ref name="Gunning"/>.  Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end<ref name="Frye">PMID:20465283</ref>.  The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin)<ref name="Gunning"/><ref name="Whitby">PMID:10651038</ref>.  A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.
 <br />
-Its role in muscle mechanics has been well established as it is a major regulatory component of the contractile apparatus, but its role in non-muscle systems is becoming evermore clear.  In mammals, there are at least 40 known isoforms, which are generated by alternative splicing of multiple genes.  These isoforms in non-muscle systems contribute to actin's stability by increasing filament rigidity and protecting the filament from actin severing proteins, like [[gelsolin]] or [http://en.wikipedia.org/wiki/Cofilin cofilin]. The different isoforms also aid in recruitment of various proteins, including myosin (a family of molecular motors).  The reason for tropomyosin's diversity is not well known, but it is thought to exist to function at different developmental stages in some species as well as function in specific cells of higher multicellular organisms.
+Its role in muscle mechanics has been well established as it is a major regulatory component of the contractile apparatus, but its role in non-muscle systems is becoming evermore clear.  In mammals, there are at least 40 known isoforms, which are generated by alternative splicing of multiple genes<ref name="Gunning"/><ref name="Frye"/>.  These isoforms in non-muscle systems contribute to actin's stability by increasing filament rigidity and protecting the filament from actin severing proteins, like [[gelsolin]] or [http://en.wikipedia.org/wiki/Cofilin cofilin]. The different isoforms also aid in recruitment of various proteins, including myosin (a family of molecular motors)<ref name="Clayton"/><ref name="Stark"/>.  The reason for tropomyosin's diversity is not well known, but it is thought to exist to function at different developmental stages in some species as well as function in specific cells of higher multicellular organisms<ref name="Gunning"/>.
 <br />
 <br />
@@ Line 13: / Line 13: @@
 #'''Superfamily:''' tropomyosin
 #'''Family:''' pig [[http://www.pdb.org/pdb/explore/explore.do?structureId=1C1G 1c1g]]
-<Structure load='1c1g' size='400' frame='true' align='left' caption='Tropomyosin Dimer: Click on Green Links (right) to see hydrophobic and ionic interactions between the two alpha helices' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'/> [[Image:Helical Wheel Respresentation of Tropomyosin.jpg | thumb | right | 333x200px | alt text | '''Helical Wheel Diagram Representation of Tropopomyosin:'''  The coiled-coil dimer is stabilized by hydrophobic and ionic interactions (red=hydrophobic, blue=polar & green=charged).]] Categorization of tropomyosin's <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'>coiled-coil</scene> describes a unique pattern of amino acids within the primary structure of the alpha helices that comprise the dimer interface.  The unique amino acid pattern, found within all coiled-coil proteins, is a heptad repeat, which follows a similar pattern to: '''H-P-P-H-C-P-C''', where H is hydrophobic, P is polar and C is charged.  This heptad repeat forms a right handed alpha helical secondary structure (see right for alpha helix secondary structure).  This alpha helix is special in that it forms a hydrophobic strip along one side, which will interface with an adjacent alpha helix that also contains the heptad repeat and hydrophobic strip.  These strips aid in the dimerization of tropomyosin and is important in the characteristic coiled-coil domain.
+<Structure load='1c1g' size='400' frame='true' align='left' caption='Tropomyosin Dimer: Click on Green Links (right) to see hydrophobic and ionic interactions between the two alpha helices' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'/> [[Image:Helical Wheel Respresentation of Tropomyosin.jpg | thumb | right | 333x200px | alt text | '''Helical Wheel Diagram Representation of Tropopomyosin:'''  The coiled-coil dimer is stabilized by hydrophobic and ionic interactions (red=hydrophobic, blue=polar & green=charged)Image Reconstructed from <ref name="Gunning"/>.]] Categorization of tropomyosin's <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2'>coiled-coil</scene> describes a unique pattern of amino acids within the primary structure of the alpha helices that comprise the dimer interface<ref name="Gunning"/>.  The unique amino acid pattern, found within all coiled-coil proteins, is a heptad repeat, which follows a similar pattern to: '''H-P-P-H-C-P-C''', where H is hydrophobic, P is polar and C is charged<ref name="Gunning"/><ref name="Whitby"/>.  This heptad repeat forms a right-handed alpha helical secondary structure (see right for alpha helix secondary structure)<ref name="Gunning"/>.  This alpha helix is special in that it forms a hydrophobic strip along one side, which will interface with an adjacent alpha helix that also contains the heptad repeat and hydrophobic strip.  These strips aid in the dimerization of tropomyosin and is important in the characteristic coiled-coil domain.
 <br />
-This coiled-coil domain is represented as a helical wheel diagram (see right), whereby the four amino acids (two from each alpha chain) that are adjacent to each other contribute to a <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_hydrophobic_aa/4'>hydrophobic interaction</scene>, represented in red, while the four amino acids (two from each alpha chain) flanking the hydrophobic core provide an <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_ionic_interaction/2'>ionic interaction</scene>, or salt-bridge represented as green.  Both the hydrophobic and ionic interactions contribute to the stability of the dimer.
+This coiled-coil domain is represented as a helical wheel diagram (see right), whereby the four amino acids (two from each alpha chain) that are adjacent to each other contribute to a <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_hydrophobic_aa/4'>hydrophobic interaction</scene>, represented in red, while the four amino acids (two from each alpha chain) flanking the hydrophobic core provide an <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_ionic_interaction/2'>ionic interaction</scene>, or salt-bridge represented as green.  Both the hydrophobic and ionic interactions contribute to the stability of the dimer<ref name="Gunning"/><ref name="Whitby"/>.
 <br />
 <br />
-The amino acids from each alpha chain interact with each other uniquely in that side chains of the helices interfacing will pack together in a knobs in holes arrangement.  This is accomplished by the ridges of one helix fitting between the grooves (between amino acids) of the adjacent helix.  This packing allows for the two alpha helices to wrap tightly around each other in a left handed supercoil conformation further stabilizing the tropomyosin dimer.
+The amino acids from each alpha chain interact with each other uniquely in that side chains of the helices interfacing will pack together in a knobs in holes arrangement<ref name="Gunning"/>.  This is accomplished by the ridges of one helix fitting between the grooves (between amino acids) of the adjacent helix.  This packing allows for the two alpha helices to wrap tightly around each other in a left handed supercoil conformation further stabilizing the tropomyosin dimer<ref name="Gunning"/>.
 <br />
 <br />
-Tropomyosin, as mentioned above, will form a long polymer along the length of actin in a head-to-tail overlap.  <Structure load='3mtu' size='400' frame='true' align='right' caption='Tropomyosin end-to-end overlap region [http://www.rcsb.org/pdb/explore/explore.do?structureId=3MTU (3MTU)]' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'/>This <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'>overlap region</scene> occurs as the amino acids from the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_c_d/1'>N-terminus</scene> of one dimer overlaps with the amino acids of the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b/3'>C-terminus</scene> of another dimer.  There are several <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b_e_f/1'>intermolecular contacts</scene> in the overlap region, which consist of ionic, hydrophobic and non-polar interactions.  Interestingly, the most variation seen among tropomyosin isoforms is in the overlap region, which will affect polymer formation along the actin filament.
+Tropomyosin, as mentioned above, will form a long polymer along the length of actin in a head-to-tail overlap<ref name="Frye"/>.  <Structure load='3mtu' size='400' frame='true' align='right' caption='Tropomyosin end-to-end overlap region [http://www.rcsb.org/pdb/explore/explore.do?structureId=3MTU (3MTU)]' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'/>This <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'>overlap region</scene> occurs as the amino acids from the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_c_d/1'>N-terminus</scene> of one dimer overlaps with the amino acids of the <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b/3'>C-terminus</scene> of another dimer.  There are several <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap_a_b_e_f/1'>intermolecular contacts</scene> in the overlap region, which consist of ionic, hydrophobic and non-polar interactions<ref name="Frye"/>.  Interestingly, the most variation seen among tropomyosin isoforms is in the overlap region, which will affect polymer formation along the actin filament<ref name="Frye"/>.
 <br />
-== Post-Translational Modifications ==
+=== Post-Translational Modifications ===
 There are two types of post-translational modifications to tropomyosin: acetylation and phosphorylation.
 == Tropomyosin in Muscle and Non-Muscle Systems==
-Muscle tissue is comprised of many muscle fibers or cells.  Those muscle fibers consist of myofibrils that contain a series of contractile units called sarcomeres.  Within this unit contains thick filaments, comprised mainly of [[myosin]], and thin filaments, which contains [[actin]], tropomyosin and [[troponin]].  Tropomyosin in striated muscle systems (skeletal and cardiac) acts to inhibit the myosin cross-bridges from binding to the myosin binding site on thin filaments, this tropomyosin state is in the "Blocked" position.  When the muscle is stimulated, there is a rise in intracellular calcium stemming from a cascade of cellular processes.  As the calcium is bathing the sarcomere, it will bind to the troponin complex, which is bound to both actin and tropomyosin.  The troponin will displace the tropomyosin from a "Blocked" to a "Closed" position.  This transition allows the myosin head to interact weakly with the myosin binding site.  The tropomyosin is displaced to its final position, "Open" state, along actin filament as myosin binds to its site.  These three tropomyosin states along the filament is referred to as the three state model. As the intracellular calcium concentration falls, the troponin no longer is able to displace tropomyosin and it will transition back to the "Blocked" state.
+Muscle tissue is comprised of many muscle fibers or cells.  Those muscle fibers consist of myofibrils that contain a series of contractile units called sarcomeres.  Within this unit contains thick filaments, comprised mainly of [[myosin]], and thin filaments, which contains [[actin]], tropomyosin and [[troponin]].  Tropomyosin in striated muscle systems (skeletal and cardiac) acts to inhibit the myosin cross-bridges from binding to the myosin binding site on thin filaments, this tropomyosin state is in the "Blocked" position<ref name="Lehman">PMID:19341744</ref>.  When the muscle is stimulated, there is a rise in intracellular calcium stemming from a cascade of cellular processes.  As the calcium is bathing the sarcomere, it will bind to the troponin complex, which is bound to both actin and tropomyosin<ref name="Tyska">PMID:11810692</ref>.  The troponin will displace the tropomyosin from a "Blocked" to a "Closed" position<ref name="Lehman"/>.  This transition allows the myosin head to interact weakly with the myosin binding site.  The tropomyosin is displaced to its final position, "Open" state, along actin filament as myosin binds to its site<ref name="Lehman"/>.  These three tropomyosin states along the filament is referred to as the three state model<ref name="Lehman"/>. As the intracellular calcium concentration falls, the troponin no longer is able to displace tropomyosin and it will transition back to the "Blocked" state<ref name="Lehman"/>.
 <br />
 <br />