Dilated cardiomyopathy mutation in beta-cardiac myosin enhances actin activation of the power stroke and phosphate release.

ABSTRACT: Inherited mutations in human beta-cardiac myosin (M2β) can lead to severe forms of heart failure. The E525K mutation in M2β is associated with dilated cardiomyopathy (DCM) and was found to stabilize the interacting heads motif (IHM) and autoinhibited super-relaxed (SRX) state in dimeric heavy meromyosin. However, in monomeric M2β subfragment 1 (S1) we found that E525K enhances (3-fold) the maximum steady-state actin-activated ATPase activity (k_cat) and decreases (6-fold) the actin concentration at which ATPase is one-half maximal (K_ATPase). We also found a 3 to 4-fold increase in the actin-activated power stroke and phosphate release rate constants at 30 μM actin, which overall enhanced the duty ratio 3-fold. Loaded motility assays revealed that the enha

SUBMITTER: Bodt SML 

PROVIDER: S-EPMC10680644 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature