2fxm
From Proteopedia
(New page: 200px<br /> <applet load="2fxm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fxm, resolution 2.70Å" /> '''Structure of the hu...) |
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| - | [[Image:2fxm.gif|left|200px]]<br /> | + | [[Image:2fxm.gif|left|200px]]<br /><applet load="2fxm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fxm" size=" | + | |
caption="2fxm, resolution 2.70Å" /> | caption="2fxm, resolution 2.70Å" /> | ||
'''Structure of the human beta-myosin S2 fragment'''<br /> | '''Structure of the human beta-myosin S2 fragment'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Myosin II is the major component of the muscle thick filament. It consists | + | Myosin II is the major component of the muscle thick filament. It consists of two N-terminal S1 subfragments ("heads") connected to a long dimeric coiled-coil rod. The rod is in itself twofold symmetric, but in the filament, the two heads point away from the filament surface and are therefore not equivalent. This breaking of symmetry requires the initial section of the rod, subfragment 2 (S2), to be relatively flexible. S2 is an important functional element, involved in various mechanisms by which the activity of smooth and striated muscle is regulated. We have determined crystal structures of the 126 N-terminal residues of S2 from human cardiac beta-myosin II (S2-Delta), of both WT and the disease-associated E924K mutant. S2-Delta is a straight parallel dimeric coiled coil, but the N terminus of one chain is disordered in WT-S2-Delta due to crystal contacts, indicative of unstable local structure. Bulky noncanonical side chains pack into a/d positions of S2-Delta's N terminus, leading to defined local asymmetry and axial stagger, which could induce nonequivalence of the S1 subfragments. Additionally, S2 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Delta, the first of which may provide a binding interface for the "blocked head" of smooth muscle myosin in the OFF state. The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C. |
==About this Structure== | ==About this Structure== | ||
| - | 2FXM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2FXM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HG:'>HG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FXM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Gautel, M.]] | [[Category: Gautel, M.]] | ||
[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
| - | [[Category: Thoma, N | + | [[Category: Thoma, N H.]] |
| - | [[Category: Wray, J | + | [[Category: Wray, J S.]] |
[[Category: HG]] | [[Category: HG]] | ||
[[Category: coiled coil (dimeric]] | [[Category: coiled coil (dimeric]] | ||
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[[Category: thick filament]] | [[Category: thick filament]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:26:07 2008'' |
Revision as of 15:26, 21 February 2008
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Structure of the human beta-myosin S2 fragment
Overview
Myosin II is the major component of the muscle thick filament. It consists of two N-terminal S1 subfragments ("heads") connected to a long dimeric coiled-coil rod. The rod is in itself twofold symmetric, but in the filament, the two heads point away from the filament surface and are therefore not equivalent. This breaking of symmetry requires the initial section of the rod, subfragment 2 (S2), to be relatively flexible. S2 is an important functional element, involved in various mechanisms by which the activity of smooth and striated muscle is regulated. We have determined crystal structures of the 126 N-terminal residues of S2 from human cardiac beta-myosin II (S2-Delta), of both WT and the disease-associated E924K mutant. S2-Delta is a straight parallel dimeric coiled coil, but the N terminus of one chain is disordered in WT-S2-Delta due to crystal contacts, indicative of unstable local structure. Bulky noncanonical side chains pack into a/d positions of S2-Delta's N terminus, leading to defined local asymmetry and axial stagger, which could induce nonequivalence of the S1 subfragments. Additionally, S2 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Delta, the first of which may provide a binding interface for the "blocked head" of smooth muscle myosin in the OFF state. The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C.
About this Structure
2FXM is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment., Blankenfeldt W, Thoma NH, Wray JS, Gautel M, Schlichting I, Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17713-7. Epub 2006 Nov 9. PMID:17095604
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