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.; Harris, Samantha P.

doi:10.1038/s41467-024-46957-7

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

Journal Article · 22 March 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-46957-7 · OSTI ID:2470141

^[1]; Engels, Nichlas M. ^[2]; Kuehn, Michel N. ^[1]; Nissen, Devin ^[3];

^[2];

^[3]; Irving, Thomas C. ^[3];

^[4];

^[2]

University of Muenster (Germany); Accelerated Muscle Biotechnologies Consultants, Boston, MA (United States)
University of Arizona, Tucson, AZ (United States)
Illinois Institute of Technology, Chicago, IL (United States)
University of Muenster (Germany)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: American Heart Association; German Research Foundation; IZKF Münster; National Institute of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470141

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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