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

Anthony L HesselNichlas M EngelsMichel N KuehnDevin NissenRachel L SadlerWeikang MaThomas C IrvingWolfgang A LinkeSamantha P Harris
Published in: Nature communications (2024)
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.
Keyphrases
  • binding protein
  • skeletal muscle
  • high resolution
  • insulin resistance
  • type diabetes
  • smooth muscle
  • metabolic syndrome
  • gene expression
  • magnetic resonance
  • dna binding
  • crystal structure