PDF(Pubmed)
Abstract：
Myosin binding protein C (MyBP-C) is an accessory protein of the thick filament in vertebrate cardiac muscle arranged over 9 stripes of intervals of 430 Å in each half of the A-band in the region called the C-zone. Mutations in cardiac MyBP-C are a leading cause of hypertrophic cardiomyopathy the mechanism of which is unknown. It is a rod-shaped protein composed of 10 or 11 immunoglobulin- or fibronectin-like domains labelled C0 to C10 which binds to the thick filament via its C-terminal region. MyBP-C regulates contraction in a phosphorylation dependent fashion that may be through binding of its N-terminal domains with myosin or actin. Understanding the 3D organisation of MyBP-C in the sarcomere environment may provide new light on its function. We report here the fine structure of MyBP-C in relaxed rat cardiac muscle by cryo-electron tomography and subtomogram averaging of refrozen Tokuyasu cryosections. We find that on average MyBP-C connects via its distal end to actin across a disc perpendicular to the thick filament. The path of MyBP-C suggests that the central domains may interact with myosin heads. Surprisingly MyBP-C at Stripe 4 is different; it has weaker density than the other stripes which could result from a mainly axial or wavy path. Given that the same feature at Stripe 4 can also be found in several mammalian cardiac muscles and in some skeletal muscles, our finding may have broader implication and significance. In the D-zone, we show the first demonstration of myosin crowns arranged on a uniform 143 Å repeat.
摘要：
肌球蛋白结合蛋白C（MyBP-C）是脊椎动物心肌中粗丝的辅助蛋白，在称为C区的A带的每一半中，以9条间隔430的间隔排列。心脏MyBP-C的突变是肥厚型心肌病的主要原因，其机制尚不清楚。它是一种杆状蛋白，由10或11个标记为C0至C10的免疫球蛋白或纤连蛋白样结构域组成，通过其C末端区域与粗丝结合。MyBP-C以磷酸化依赖性方式调节收缩，这可能是通过其N端结构域与肌球蛋白或肌动蛋白的结合。了解MyBP-C在肌节环境中的3D组织可能会为其功能提供新的思路。我们在这里通过冷冻电子断层扫描和再冷冻Tokuyasu冷冻切片的亚层析图平均来报告松弛大鼠心肌中MyBP-C的精细结构。我们发现，平均MyBP-C通过其远端连接到垂直于粗丝的圆盘上的肌动蛋白。MyBP-C的路径表明中央结构域可能与肌球蛋白头相互作用。令人惊讶的是,条纹4处的MyBP-C是不同的;它具有比其他条纹更弱的密度,这可由主要的轴向或波浪形路径产生。鉴于条纹4的相同特征也可以在几种哺乳动物的心肌和一些骨骼肌中发现，我们的发现可能具有更广泛的含义和意义.在D区,我们显示了肌球蛋白冠排列在均匀的143µrepeat上的首次演示。
