Institute of Physiology II, University of Muenster, Muenster, Germany.
Accelerated Muscle Biotechnologies Consultants, Boston, MA, USA.
Nat Commun. 2024 Mar 23;15(1):2628. doi: 10.1038/s41467-024-46957-7.
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), but may be loosely bound at its middle- and N-terminal end (MyBP-C) 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 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 to myofilament force production and regulation.
肌肉收缩是通过肌丝的相互作用产生的，并受到调节，以使肌肉性能与需求相匹配。肌球蛋白结合蛋白 C（MyBP-C）是一种长而灵活的蛋白质，其 C 末端（MyBP-C）与粗丝紧密结合，但在其中间和 N 末端（MyBP-C）可能与肌球蛋白头部和/或细丝松散结合。MyBP-C 被认为通过调节肌球蛋白马达来控制肌肉收缩，因为突变会导致衰弱性疾病。我们使用力学和小角度 X 射线衍射的组合来研究在通透的骨骼肌中快速 MyBP-C 的 MyBP-C 结构域的即时和选择性去除。我们表明，切割会导致交联动力学和肌丝的被动结构特征的改变，这些改变表明肌球蛋白头部向 ON 状态的转变，突出了 MyBP-C 对肌丝力产生和调节的重要性。
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