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Structure of actomyosin rigor complex at 5.2-Å resolution and insights into the ATPase cycle mechanism

 Osaka University announced on January 11, 2017 that a study group led by Prof. Keiichi Namba (Graduate School of Frontier Biosciences) has clarified the structure of actomyosin complex at 5.2-Å resolution to get the insights into the ATPase cycle mechanism. The study was published in Nature Communications*.

 Muscle is the molecular motor that converts chemical energy to mechanical work. Muscle contraction occurs through mutual sliding of thick myosin filaments and thin actin filaments. The sliding force is generated via cyclic interactions of myosin heads with actin molecules on the thin filaments. At the myosin head, actin filaments are coupled with myosin with ATP binding. Myosin head is an ATPase that regulates the cyclic association and dissociation of myosin with actin filament. Although ATPase hydrolyzes ATP immediately after the binding, how quickly the hydrolysis products are released from the nucleotide-binding pocket is still unclear due to the difficulty in observing rigor structure of actomyosin at high resolution. 

 In this study, the research group has succeeded in obtaining the image of mammalian skeletal muscle at 5.2 Å resolution and analyzed the structure by using electron cryomicroscopy. It became clear that myosin changes its conformation largely during the ATPase-coupled reaction cycle of actomyosin. This conformational change widely opens the nucleotide-binding pocket to release the hydrolysis products. In this weak binding state, asymmetrical structure could function as a Brownian ratchet that converts the random thermal motion of myosin and actin toward a favored direction.

* Takashi Fujii and Keiichi Namba, "Structure of actomyosin rigour complex at 5.2-Å resolution and insights into the ATPase cycle mechanism", Nature Communications, Vol. 8, Article number: 13969 (2017), doi: 10.1038/ncomms13969; Published online: 09 January 2017