Effects of cardiomyopathy-linked mutations K15N and R21H in tropomyosin on thin-filament regulation and pointed-end dynamics.

ABSTRACT: Missense mutations K15N and R21H in striated muscle tropomyosin are linked to dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), respectively. Tropomyosin, together with the troponin complex, regulates muscle contraction and, along with tropomodulin and leiomodin, controls the uniform thin-filament lengths crucial for normal sarcomere structure and function. We used Förster resonance energy transfer to study effects of the tropomyosin mutations on the structure and kinetics of the cardiac troponin core domain associated with the Ca²⁺-dependent regulation of cardiac thin filaments. We found that the K15N mutation desensitizes thin filaments to Ca²⁺ and slows the kinetics of structural changes in troponin induced by Ca²⁺ dissociation from tro

SUBMITTER: Ly T 

PROVIDER: S-EPMC6589558 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature