A gain-of-function mutation in the M-domain of cardiac myosin-binding protein-C increases binding to actin.

ABSTRACT: The M-domain is the major regulatory subunit of cardiac myosin-binding protein-C (cMyBP-C) that modulates actin and myosin interactions to influence muscle contraction. However, the precise mechanism(s) and the specific residues involved in mediating the functional effects of the M-domain are not fully understood. Positively charged residues adjacent to phosphorylation sites in the M-domain are thought to be critical for effects of cMyBP-C on cross-bridge interactions by mediating electrostatic binding with myosin S2 and/or actin. However, recent structural studies revealed that highly conserved sequences downstream of the phosphorylation sites form a compact tri-helix bundle. Here we used site-directed mutagenesis to probe the functional significance of charged residues adjacent to the ph

SUBMITTER: Bezold KL 

PROVIDER: S-EPMC3724610 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature