Dynamics of β-cardiac myosin between the super-relaxed and disordered-relaxed states.

ABSTRACT: The super-relaxed (SRX) state of myosin ATPase activity is critical for striated muscle function, and its dysregulation is linked to cardiomyopathies. It is unclear whether the SRX state exchanges readily with the disordered-relaxed (DRX) state and whether the SRX state directly corresponds to the folded back interacting-heads motif. Using recombinant β-cardiac heavy meromyosin and subfragment 1, which cannot form the interacting-heads motif, we show that the SRX and DRX populations transition at a rate substantially faster than the ATP turnover rate, dependent on myosin head-tail interactions. Some mutations which cause hypertrophic or dilated cardiomyopathies alter the SRX-DRX equilibrium, but not all mutations. The cardiac myosin inhibitor mavacamten slows nucleotide release by an equal

SUBMITTER: Cail RC 

PROVIDER: S-EPMC12023885 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature