2fxm
From Proteopedia
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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 HG 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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