Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.

ABSTRACT:

Background

Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca²⁺ homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation in the sarcomere-gene-positive preclinical HCM cohort, which suggests the potential involvement of myofilament regulators in relaxation. A molecular-level understanding of mechanism(s) at the level of the myofilament is lacking. We hypothesized that mutation-specific, allosterically mediated, changes to the cTnC (cardiac troponin C)-cTnI (cardiac troponin I) interface can account for the development of early-onset diastolic dysfunction via decreased PKA accessibility to cTnI.

Methods

HCM mutati

SUBMITTER: Lynn ML 

PROVIDER: S-EPMC11502267 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature