The actin-myosin interface
- Biophysics Group, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
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Edited* by James A. Spudich, Stanford University School of Medicine, Stanford, CA, and approved April 30, 2010 (received for review March 19, 2010)
Abstract
In order to understand the mechanism of muscle contraction at the atomic level, it is necessary to understand how myosin binds to actin in a reversible way. We have used a novel molecular dynamics technique constrained by an EM map of the actin-myosin complex at 13-Å resolution to obtain an atomic model of the strong-binding (rigor) actin-myosin interface. The constraining force resulting from the EM map during the molecular dynamics simulation was sufficient to convert the myosin head from the initial weak-binding state to the strong-binding (rigor) state. Our actin-myosin model suggests extensive contacts between actin and the myosin head (S1). S1 binds to two actin monomers. The contact surface between actin and S1 has increased dramatically compared with previous models. A number of loops in S1 and actin are involved in establishing the interface. Our model also suggests how the loop carrying the critical Arg 405 Glu mutation in S1 found in a familial cardiomyopathy might be functionally involved.
Footnotes
- 1To whom correspondence should be addressed. E-mail: Michael.Lorenz{at}mpimf-heidelberg.mpg.de.
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Author contributions: M.L. and K.C.H. designed research; M.L. performed research; M.L. and K.C.H. analyzed data; and M.L. and K.C.H. wrote the paper.
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The authors declare no conflict of interest.
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*This Direct Submission article had a prearranged editor.
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This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1003604107/-/DCSupplemental.
