Structural mechanism of the recovery stroke in the Myosin molecular motor
- Departments of *Computational Biochemistry and ¶Computational Molecular Biophysics, Interdisciplinary Center for Scientific Computing, Universität Heidelberg, 69120 Heidelberg, Germany; and §Max Planck Institut für Medizinische Forschung, 69120 Heidelberg, Germany
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Edited by Thomas D. Pollard, Yale University, New Haven, CT, and approved March 7, 2005 (received for review November 24, 2004)
Abstract
The power stroke pulling myosin along actin filaments during muscle contraction is achieved by a large rotation (≈60°) of the myosin lever arm after ATP hydrolysis. Upon binding the next ATP, myosin dissociates from actin, but its ATPase site is still partially open and catalytically off. Myosin must then close and activate its ATPase site while returning the lever arm for the next power stroke. A mechanism for this coupling between the ATPase site and the distant lever arm is determined here by generating a continuous series of optimized intermediates between the crystallographic end-states of the recovery stroke. This yields a detailed structural model for communication between the catalytic and the force-generating regions that is consistent with experimental observations. The coupling is achieved by an amplifying cascade of conformational changes along the relay helix lying between the ATPase and the domain carrying the lever arm.
Footnotes
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↵ † To whom correspondence should be addressed. E-mail: stefan.fischer{at}iwr.uniheidelberg.de.
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↵ ‡ Present address: Institut für Pharmazeutische Chemie, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle (Saale), Germany.
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Author contributions: S.F. designed research; B.W. and D.H. performed research; S.F., B.W., and K.C.H. analyzed data; and S.F. and J.C.S. wrote the paper.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: γP, γ phosphate; CPR, Conjugate Peak Refinement; SH1, Src homology 1.
- Copyright © 2005, The National Academy of Sciences
