Autoinhibition and activation mechanisms revealed by the triangular-shaped structure of myosin Va.

ABSTRACT: As the prototype of unconventional myosin motor family, myosin Va (MyoVa) transport cellular cargos along actin filaments in diverse cellular processes. The off-duty MyoVa adopts a closed and autoinhibited state, which can be relieved by cargo binding. The molecular mechanisms governing the autoinhibition and activation of MyoVa remain unclear. Here, we report the cryo-electron microscopy structure of the two full-length, closed MyoVa heavy chains in complex with 12 calmodulin light chains at 4.78-Å resolution. The MyoVa adopts a triangular structure with multiple intra- and interpolypeptide chain interactions in establishing the closed state with cargo binding and adenosine triphosphatase activity inhibited. Structural, biochemical, and cellular analyses uncover an asymmetric autoinhibiti

SUBMITTER: Niu F 

PROVIDER: S-EPMC9733927 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature