Functional significance of HCM mutants of tropomyosin, V95A and D175N, studied with in vitro motility assays.

ABSTRACT: The majority of hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere proteins. We examined tropomyosin (Tpm)'s HCM mutants in humans, V95A and D175N, with in vitro motility assay using optical tweezers to evaluate the effects of the Tpm mutations on the actomyosin interaction at the single molecular level. Thin filaments were reconstituted using these Tpm mutants, and their sliding velocity and force were measured at varying Ca²⁺ concentrations. Our results indicate that the sliding velocity at pCa ≥8.0 was significantly increased in mutants, which is expected to cause a diastolic problem. The velocity that can be activated by Ca²⁺ decreased significantly in mutants causing a systolic problem. With sliding force, Ca²⁺ activatable for

SUBMITTER: Ishii S 

PROVIDER: S-EPMC6435021 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature