Accepted_test

Effect of hypertrophic mutations of cardiac myosin-binding protein C on actin-myosin interaction

Authors:
Anastasia Kochurova, Institute of Immunology and Physiology
Evgeniia Beldiia, Institute of Immunology and Physiology
Alexander Matyushenko, Federal Research Center of Biotechnology RAS
Sergey Bershitsky, Institute of Immunology and Physiology
Daniil Shchepkin, 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.