PDF(Pubmed)
Abstract：
In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2-/-) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2-/- fibers present deficits in force production and calcium sensitivity. Structurally, passive C2-/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2-/-, which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.
摘要：
在横纹肌中，肌节蛋白肌球蛋白结合蛋白C（MyBP-C）与肌球蛋白粗丝结合，并有望使肌球蛋白头部稳定在对接位置，这限制了跨桥的形成。这里,我们使用纯合Mybpc2敲除(C2-/-)小鼠品系从快速骨骼肌中去除快速同工型MyBP-C,然后与小角度X射线衍射平行进行机械功能研究以评估肌丝结构.我们报告说，C2-/-纤维在力产生和钙敏感性方面存在缺陷。在结构上,被动C2-/-纤维表达肌球蛋白头构象的肌节长度无关和依赖性调节，随着肌球蛋白头部向肌动蛋白的转移。在较短的肌节长度，细丝以C2-/-轴向延伸，我们假设这是由于低级交叉桥的数量增加。这些发现提供了可测试的机制来解释与MyBP-C相关的衰弱性疾病的病因。
