BIOPHYSICS
Review Article
3-D structural analysis of the crucial intermediate of skeletal muscle myosin and its role in revised actomyosin cross-bridge cycle
Eisaku Katayama
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Volume 10 (2014) Pages 89-97

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Abstract

Skeletal myosin S1 consists of two functional segments, a catalytic-domain and a lever-arm. Since the crystal structure of ADP/Vi-bound S1 exhibits a strong intramolecular flexure between two segments, inter-conversion between bent and extended forms; i.e. “tilting of the lever-arm” has been accepted as the established molecular mechanism of skeletal muscle contraction. We utilized quick-freeze deep-etch replica electron microscopy to directly visualize the structure of in vitro actin-sliding myosin, and found the existence of a novel oppositely-bent configuration, instead of the expected ADP/Vi-bound form. We also noticed that SH1–SH2 cross-linked myosin gives an aberrant appearance similar to the above structure. Since SH1–SH2-cross-linked myosin is a well-studied analogue of the transient intermediate of the actomyosin cross-bridge cycle, we devised a new image-processing procedure to define the relative view-angles between the catalytic-domain and the lever-arm from those averaged images, and built a 3-D model of the new conformer. The lever-arm in that model was bent oppositely to the ADP/Vi-bound form, in accordance with observed actin-sliding cross-bridge structure. Introducing this conformer as the crucial intermediate that transiently appears during sliding, we propose a revised scheme of the cross-bridge cycle. In the scenario, the novel conformer keeps actin-binding in two different modes until it forms a primed configuration. The final extension of the lever-arm back to the original rigor-state constitutes the “power-stroke”. Various images observed during sliding could be easily interpreted by the new conformer. Even the enigmatic behavior of the cross-bridges reported as “loose chemo-mechanical coupling” might be adequately explained under some assumptions.

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© 2014 THE BIOPHYSICAL SOCIETY OF JAPAN
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