<i>N</i>-terminal fragment of cardiac myosin binding protein C modulates cooperative mechanisms of the thin filament activation in the atria and ventricles

Abstract

Cardiac myosin binding protein C (cMyBP-C) is one of the essential control components of the myosin cross-bridge cycle. The C-terminal part of cMyBP-C lies on the surface of the thick filament, and its N-terminal part interacts with actin, myosin, and tropomyosin, affecting both the kinetics of the ATP hydrolysis cycle and the lifetime of the cross bridge, as well as the calcium regulation of actin-myosin interaction, thereby modulating the contractile function of the myocardium. The role of cMyBP-C in atrial contraction is poorly studied. We examined the effect of the N-terminal C0-m-C2 (C0-C2) fragment of cMyBP-C on actin-myosin interaction using ventricular and atrial myosin in anin vitromotility assay. The C0-C2 fragment of cMyBP-C significantly reduced the maximum sliding velocity of thin filaments on both myosin isoforms and increased the calcium sensitivity of actin-myosin interaction. The C0-C2 fragment had different effects on the kinetics of nucleotide, ATP, and ADP exchange, increasing the affinity of ventricular myosin for ADP and decreasing the affinity of atrial myosin. The effect of the C0-C2 fragment on the activation of the thin filament depended on the myosin isoforms. Atrial myosin activates the thin filament less strongly than ventricular myosin, and the C0-C2 fragment makes these differences in myosin isoforms more pronounced.