Cryo-EM structure of shutdown human non-muscle myosin 2A

Casas Mao, D.; Carrington, G.; Peckham, M.

doi:10.1101/2025.10.15.682586

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bioRxiv · 10.1101/2025.10.15.682586

Cryo-EM structure of shutdown human non-muscle myosin 2A

Casas Mao, D.·Carrington, G.·Peckham, M.

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Abstract

Determining the high-resolution structure of the widely expressed non-muscle myosin 2A (NM2A), in its dephosphorylated shutdown state, is important in understanding its regulation and disease roles. In shutdown molecules, the coiled-coil tail wraps around the myosin heads preventing them from forming filaments and binding to actin. We have solved the shutdown structure of NM2A to a global resolution of 3.0 [A] in the heads region, and 6.3 [A] for the whole molecule. This reveals specific ionic interactions that explain why the path of the coiled coil and the shutdown mechanism for NM2A differs from that of {beta}-cardiac myosin and provides key insight into how specific mutations likely destabilize the shutdown state, leading to disease.

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Casas Mao, D., Carrington, G., Peckham, M.. 2025-10-15. Cryo-EM structure of shutdown human non-muscle myosin 2A. https://doi.org/10.1101/2025.10.15.682586

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