The intrinsically disordered C terminus of troponin T binds to troponin C to modulate myocardial force generation.

ABSTRACT: Aberrant regulation of myocardial force production represents an early biomechanical defect associated with sarcomeric cardiomyopathies, but the molecular mechanisms remain poorly defined. Here, we evaluated the pathogenicity of a previously unreported sarcomeric gene variant identified in a pediatric patient with sporadic dilated cardiomyopathy, and we determined a molecular mechanism. Trio whole-exome sequencing revealed a de novo missense variant in TNNC1 that encodes a p.I4M substitution in the N-terminal helix of cardiac troponin C (cTnC). Reconstitution of this human cTnC variant into permeabilized porcine cardiac muscle preparations significantly decreases the magnitude and rate of isometric force generation at physiological Ca²⁺-activation levels. Computati

SUBMITTER: Johnston JR 

PROVIDER: S-EPMC6937556 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature