Accepted_test

Effect of hypertrophic mutations of cardiac myosin-binding protein C on actin-myosin interaction
by Anastasia Kochurova | Evgeniia Beldiia | Alexander Matyushenko | Sergey Bershitsky | Daniil Shchepkin | Institute of Immunology and Physiology | Institute of Immunology and Physiology | Federal Research Center of Biotechnology RAS | Institute of Immunology and Physiology | Institute of Immunology and Physiology
Abstract ID: 456
Event: BGRS-abstracts
Sections: [Sym 9] Section “Molecular Pathology, Diagnostics, and Therapeutics”

About 45% of sarcomere protein mutations associated with hypertrophic cardiomyopathies (HCM) are cardiac myosin binding protein C (cMyBP-C). The molecular mechanisms of the development of HCM with point mutations in cMyBP-C are practically not studied. We researched the effect of HCM mutations D75N, P161S, and L352P in the N-terminal part of the cMyBP-C on actin-myosin interaction in the myocardium. We found that the mutations disrupt the calcium regulation of actin-myosin interaction, which may be one of the molecular mechanisms of HCM development. The P161S mutation impairs the activation of thin filaments, and omecamtiv mecarbil, a specific activator of ventricular myosin, only partially neutralizes the negative effect of this mutation on the actin-myosin interaction.