Abstract

Muscle contraction is driven by cyclic association and dissociation of myosin head of the thick filament with thin actin filament coupled with ATP binding and hydrolysis by myosin. However, due to the absence of actomyosin rigor structure at high resolution, it still remains unclear how the strong binding of myosin to actin filament triggers the release of hydrolysis products and how ATP binding causes their dissociation. Here we report the structure of mammalian skeletal muscle actomyosin rigor complex at 5.2 Å resolution by electron cryomicroscopy. Comparison with the structures of myosin in various states shows a distinctly large conformational change that has never been observed, giving much clearer insights into the ATPase-coupled reaction cycle of actomyosin. A model of actomyosin structure in the weak binding state suggests how its asymmetric binding along actin filament could cause directionally biased thermal fluctuations of myosin and actin to work as a Brownian ratchet.