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

Hessel, Anthony L; Engels, Nichlas M; Kuehn, Michel N; Nissen, Devin; Sadler, Rachel L; Ma, Weikang; Irving, Thomas C; Linke, Wolfgang A et al. · Nat Commun · 2024

basic_science · Level V

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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<sup>C8C10</sup>), but may be loosely bound at its middle- and N-terminal end (MyBP-C<sup>C1C7</sup>) 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<sup>C1C7</sup> 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<sup>C1C7</sup> to myofilament force production and regulation.

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