Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function

• DOI: 10.1073/pnas.0808903105
• Publication Date: 2008-11-15T01:54:26Z
• Authors: Andrew E. Whitten; Cy M. Jeffries; Samantha P. Harris; Jill Trewhella
• Keywords: Models, Molecular; 0303 health sciences; Familial hypertrophic cardiomypathy; Muscles; Myosin; Muscle regulation; Heart; Hypertrophy; C protein; 0601 Biochemistry and Cell Biology; Actins; Mice; 03 medical and health sciences; Heart Function Tests; Animals; Scattering, Radiation; Small-angle scattering; Phosphorylation; Small Angle Scattering; Carrier Proteins; Actin; Neutron contrast variation

Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin.