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bioRxiv · 10.1101/2021.09.07.459262

High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism

Pospich, S.·Sweeney, L.·Houdusse, A.·Raunser, S.
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Abstract

The molecular motor myosin undergoes a series of major structural transitions during its force-producing motor cycle. The underlying mechanism and its coupling to ATP hydrolysis and actin binding is only partially understood, mostly due to sparse structural data on actin-bound states of myosin. Here, we report 26 high-resolution cryo-EM structures of the actomyosin-V complex in the strong-ADP, rigor, and a previously unseen post-rigor transition state that binds the ATP analog AppNHp. The structures reveal a high flexibility of myosin in each state and provide valuable insights into the structural transitions of myosin-V upon ADP release and binding of AppNHp, as well as the actomyosin interface. In addition, they show how myosin is able to specifically alter the structure of F-actin. The unprecedented number of high-resolution structures of a single myosin finally enabled us to assemble a nearly complete structural model of the myosin-V motor cycle and describe the molecular principles of force production.

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Pospich, S., Sweeney, L., Houdusse, A., Raunser, S.. 2021-09-07. High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism. https://doi.org/10.1101/2021.09.07.459262

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