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Chinthalapudi, Krishna, Heissler, SM Sarah M, Preller, Matthias, Sellers, JR James R, Manstein, DJ Dietmar J, (2017) ' Mechanistic Insights into the Active Site and Allosteric Communication Pathways in Human Nonmuscle Myosin-2C. ' Elife 6
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Abstract:Despite a generic, highly conserved motor domain, ATP turnover kinetics and their activation by F-actin vary greatly between myosin-2 isoforms. Here, we present a 2.25 ? crystal pre-powerstroke state (ADP?VO4) structure of the human nonmuscle myosin-2C motor domain, one of the slowest myosins characterized. In combination with integrated mutagenesis, ensemble-solution kinetics, and molecular dynamics simulation approaches, the structure reveals an allosteric communication pathway that connects the distal end of the motor domain with the active site. Disruption of this pathway by mutation of hub residue R788, which forms the center of a cluster of interactions connecting the converter, the SH1-SH2 helix, the relay helix, and the lever, abolishes nonmuscle myosin-2 specific kinetic signatures. Our results provide insights into structural changes in the myosin motor domain that are triggered upon F-actin binding and contribute critically to the mechanochemical behavior of stress fibers, actin arcs, and cortical actin-based structures.
Status: aheadofprint Type: Journal article Source: PUBMED PubMed ID: 29256864

Genes addressed in this paper
Topics in this paper
Mammalian Gene Related X
Protein Functional Domain X
Non-mammalian Gene Related X
Protein/Nucleic Acid Structure X