9Z3W

Cryo-EM structure of human nonmuscle myosin-2B, Class 1

Summary for 9Z3W

• Entry DOI: 10.2210/pdb9z3w/pdb
• EMDB information: 73793
• Descriptor: Myosin-10, Myosin light polypeptide 6, Myosin regulatory light chain 12B, ... (6 entities in total)
• Functional Keywords: myosin, atpase, motor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 533320.43

Authors

Heissler, S.M.,Chinthalapudi, K. (deposition date: 2025-11-07, release date: 2026-07-08)

Primary citation

Heissler, S.M.,Grandinetti, G.,Sellers, J.R.,Chinthalapudi, K.
Structural basis of nonmuscle myosin-2 autoinhibition mechanisms.
Nat Commun, 2026

PubMed Abstract: Nonmuscle myosin-2 (NM2) is a fundamental actin-based mechanochemical ATPase that regulates cellular architecture, migration, adhesion, and force generation across diverse biological contexts. NM2 function is tightly regulated by a structural transition between an autoinhibited monomeric (10S) conformation in which ATPase activity, actin binding, and filament assembly are coordinately suppressed and an enzymatically active, filamentous conformation. The autoinhibited conformation is critical for the spatial and temporal control of contractility in nonmuscle cells, yet structural insights into the 10S conformation remain largely elusive. Here, we report a ~53-nm elongated full-length structure of NM2B in the 10S conformation and four distinct cryo-EM structures representing the conformational landscape within the human NM2B 10S state. These structures reveal a tri-segmented tail fold that sequesters interfaces essential for actin binding and filament assembly. The asymmetric arrangement of myosin heavy and light chains provides a mechanistic foundation for understanding how regulatory post-translational modifications and disease-associated mutations shift NM2 conformational equilibria and may enable the development of structure-based interventions for cytoskeletal diseases including hearing loss, neurodegeneration, and cancer.

PubMed: 42323327
DOI: 10.1038/s41467-026-74674-w

Experimental method

ELECTRON MICROSCOPY (5.34 Å)