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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Atomic model of the human cardiac muscle myosin filament
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Atomic model of the human cardiac muscle myosin filament

机译：人心肌肌球蛋白丝的原子模型

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Of all the myosin filaments in muscle, the most important in terms of human health, and so far the least studied, are those in the human heart. Here we report a 3D single-particle analysis of electron micrograph images of negatively stained myosin filaments isolated from human cardiac muscle in the normal (undis-eased) relaxed state. The resulting 28-A resolution 3D reconstruction shows axial and azimuthal (no radial) myosin head perturbations within the 429-A axial repeat, with rotations between successive 132 A-, 148 A-, and 149 A-spaced crowns of heads close to 60°, 35°, and 25° (all would be 40° in an unperturbed three-stranded helix). We have defined the myosin head atomic arrangements within the three crown levels and have modeled the organization of myosin subfragment 2 and the possible locations of the 39 A-spaced domains of titin and the cardiac isoform of myosin-binding pro-tein-C on the surface of the myosin filament backbone. Best fits were obtained with head conformations on all crowns close to the structure of the two-headed myosin molecule of vertebrate chicken smooth muscle in the dephosphorylated relaxed state. Individual crowns show differences in head-pair tilts and subfragment 2 orientations, which, together with the observed perturbations, result in different intercrown head interactions, including one not reported before. Analysis of the interactions between the myosin heads, the cardiac isoform of myosin-binding protein-C, and titin will aid in understanding of the structural effects of mutations in these proteins known to be associated with human cardiomyopathies.
机译：就人类健康而言，肌肉中所有的肌球蛋白丝最重要，而迄今为止研究最少的是人体心脏丝。在这里，我们报告了从正常（不舒张的）松弛状态下从人心肌分离的阴性染色的肌球蛋白丝的电子显微镜图像的3D单粒子分析。所得的28-A分辨率3D重建结果显示在429-A轴向重复中出现了轴向和方位角（无径向）的肌球蛋白头部扰动，在连续的132 A-，148 A-和149 A间隔的头顶之间连续旋转了60个头°，35°和25°（在不受干扰的三链螺旋中均为40°）。我们在三个冠层水平上定义了肌球蛋白头部的原子排列，并模拟了肌球蛋白亚片段2的组织，以及39个A间隔的titin域和肌球蛋白结合蛋白-C的心脏同工型的可能位置。肌球蛋白丝骨架的表面。获得最佳拟合的是，所有冠上的头部构型均与处于脱磷酸化松弛状态的脊椎动物鸡平滑肌的双头肌球蛋白分子的结构接近。单个牙冠显示出头部对倾斜和亚碎片2方向的差异，再加上观察到的扰动，导致冠间的交互作用不同，包括以前没有报道过的。分析肌球蛋白头，肌球蛋白结合蛋白C的心脏同工型和替丁之间的相互作用，将有助于了解这些蛋白中与人类心肌病相关的突变的结构效应。

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