9IHL

Crystal Structure of the Human Nonmuscle Myosin 2A Motor Domain

Summary for 9IHL

• Entry DOI: 10.2210/pdb9ihl/pdb
• Descriptor: Myosin-9,Alpha-actinin A (2 entities in total)
• Functional Keywords: myosin, nm2a, human, motor, protein, motor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 117418.92

Authors

Heiringhoff, R.S.,Greve, J.N.,Zahn, M.,Manstein, D.J. (deposition date: 2025-02-21, release date: 2025-09-24, Last modification date: 2025-10-22)

Primary citation

Heiringhoff, R.S.,Greve, J.N.,Zahn, M.,Manstein, D.J.
Structure of the human nonmuscle myosin 2A motor domain: Insights into isoform-specific mechanochemistry.
J.Biol.Chem., 301:110691-110691, 2025

PubMed Abstract: Non-muscle myosin 2A (NM2A) is the predominant myosin isoform in non-muscle cells. Together with its paralogues NM2B and NM2C, NM2A enables tension and force generation, driving essential cellular processes such as membrane protrusion and retraction, directed migration, adhesion and cytokinesis. The NM2 isoforms display paralogue-specific mechanochemical characteristics that support their specific cellular functions. Here, we determined the structure of the human NM2A motor domain, addressing a critical gap in understanding myosin family diversification. Based on our experimentally resolved 2.1 Å structure of the NM2A motor domain in its nucleotide-free state, we demonstrate, through integrative modeling of NM2-actin complexes and molecular dynamics simulations, how sequence differences between NM2A and NM2B underpin their functional specialization. Loop2 emerges as a critical determinant of isoform-specific behavior. Comparative analysis of ATP interaction fingerprints across NM2 isoforms reveals a conserved ATP binding mechanism. These findings illuminate an allosteric energy transduction pathway that connects sequence variation to actin-binding dynamics, providing mechanistic insight into isoform-specific cytoskeletal functions.

PubMed: 40939649
DOI: 10.1016/j.jbc.2025.110691

Experimental method

X-RAY DIFFRACTION (2.02 Å)