Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads.

ABSTRACT: Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-C^C8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-C^C1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-C^C1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-C^C1C7 to myofilament force production and regulation.

SUBMITTER: Hessel AL 

PROVIDER: S-EPMC10960836 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature