Cardiomyopathy-linked myosin regulatory light chain mutations disrupt myosin strain-dependent biochemistry.

ABSTRACT: Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in sarcomeric proteins including the myosin regulatory light chain (RLC). Two such FHC mutations, R58Q and N47K, located near the cationic binding site of the RLC, have been identified from population studies. To examine the molecular basis for the observed phenotypes, we exchanged endogenous RLC from native porcine cardiac myosin with recombinant human ventricular wild type (WT) or FHC mutant RLC and examined the ability of the reconstituted myosin to propel actin filament sliding using the in vitro motility assay. We find that, whereas the mutant myosins are indistinguishable from the controls (WT or native myosin) under unloaded conditions, both R58Q- and N47K-exchanged myosins show reductions in force and power output co

SUBMITTER: Greenberg MJ 

PROVIDER: S-EPMC2951453 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature