7YV9

Cryo-EM structure of full-length Myosin Va in the autoinhibited state

Summary for 7YV9

• Entry DOI: 10.2210/pdb7yv9/pdb
• EMDB information: 34121
• Descriptor: Unconventional myosin-Va, Calmodulin-1 (2 entities in total)
• Functional Keywords: intracellular trafficking, molecular motor, myosin, autoinhibition, motor protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 16
• Total formula weight: 1052812.70

Authors

Niu, F.,Wei, Z. (deposition date: 2022-08-19, release date: 2022-12-21, Last modification date: 2024-07-03)

Primary citation

Niu, F.,Liu, Y.,Sun, K.,Xu, S.,Dong, J.,Yu, C.,Yan, K.,Wei, Z.
Autoinhibition and activation mechanisms revealed by the triangular-shaped structure of myosin Va.
Sci Adv, 8:eadd4187-eadd4187, 2022

PubMed 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 autoinhibition mechanism, in which the cargo-binding sites in the two MyoVa heavy chains are differently protected. Thus, specific and efficient MyoVa activation requires coincident binding of multiple cargo adaptors, revealing an intricate and elegant activity regulation of the motor in response to cargos.

PubMed: 36490350
DOI: 10.1126/sciadv.add4187

Experimental method

ELECTRON MICROSCOPY (4.78 Å)