Understanding the Organisation and Role of Myosin Binding Protein C in Normal Striated Muscle by Comparison with MyBP-C Knockout Cardiac Muscle
Understanding the Organisation and Role of Myosin Binding Protein C in Normal Striated Muscle by Comparison with MyBP-C Knockout Cardiac Muscle
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DOI：
10.1016/j.jmb.2008.09.013
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发表时间：
2008-12-05
影响因子：
5.6
通讯作者：
Moss, Richard L.
中科院分区：
文献类型：
--
作者：
Luther, Pradeep K.;Bennett, Pauline M.;Moss, Richard L.
肌球蛋白结合蛋白C（MyBP-C）是横纹肌粗肌丝的组成部分。心脏基因突变是家族性肥厚型心肌病的主要病因，这一证据揭示了这种蛋白的重要性。在这里，我们研究MyBP-C在心肌和骨骼肌A带中的分布，并将其与MyBP-C缺陷小鼠心肌中的A带结构进行比较。我们已经使用了一种新的平均技术，以获得轴向密度分布的A带保存完好的标本的电子显微照片。我们发现，心脏和骨骼的A带是非常相似的，长度为1.58 +/- 0.01 μ m。在正常的心肌和骨骼肌中，分布非常相似，清楚地显示了一系列的11个突出的辅助蛋白条纹在每一半的A带轴向间隔在43 nm的间隔，并开始在裸区的边缘。我们用抗体标记的方法证明了MyBP-C在心肌中的分布部位是远侧九条带。正如预期的那样，这些条纹在敲除小鼠心脏中受到相当大的抑制。松弛肌肉中粗肌丝表面的肌球蛋白头被认为是以三股准螺旋排列的，平均轴向横桥间距为14.3 nm，螺旋重复为43 nm。在肌肉的X射线衍射图中，在43 nm的数量级上，额外的禁止反射被解释为是由于肌球蛋白头的某些水平的轴向扰动。然而，在MyBP-C缺乏的心脏中，这些额外的反射很弱或不存在，这表明它们是由于MyBP-C本身或MyBP-C与MyBP-C的存在所带来的头部扰动的组合。(c)2008爱思唯尔有限公司版权所有。
Myosin binding protein C (MyBP-C) is a component of the thick filament of striated muscle. The importance of this protein is revealed by recent evidence that mutations in the cardiac gene are a major cause of familial hypertrophic cardiomyopathy. Here we investigate the distribution of MyBP-C in the A-bands of cardiac and skeletal muscles and compare this to the A-band structure hi cardiac muscle of MyBP-C-deficient mice. We have used a novel averaging technique to obtain the axial density distribution of A-bands in electron micrographs of well-preserved specimens. We show that cardiac and skeletal A-bands are very similar, with a length of 1.58 +/- 0.01 mu m. In normal cardiac and skeletal muscle, the distributions are very similar, showing clearly the series of 11 prominent accessory protein stripes in each half of the A-band spaced axially at 43-nm intervals and starting at the edge of the bare zone. We show by antibody labelling that in cardiac Muscle the distal nine stripes are the location of MyBP-C. These stripes are considerably Suppressed in the knockout mouse hearts as expected. Myosin heads on the surface of the thick filament in relaxed Muscle are thought to be arranged in a three-stranded quasi-helix with a mean 14.3-nm axial cross bridge spacing and a 43 nm helix repeat. Extra forbidden meridional reflections, at orders of 43 nm, in X-ray diffraction patterns of muscle have been interpreted as due to an axial perturbation of some levels of myosin heads. However, in the MyBP-C-deficient hearts these extra meridional reflections are weak or absent, suggesting that they are due to MyBP-C itself or to MyBP-C in combination with a head perturbation brought about by the presence of MyBP-C. (c) 2008 Elsevier Ltd. All rights reserved.