Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
Cell. 2012 Jul 20;150(2):327-38. doi: 10.1016/j.cell.2012.05.037.
Regulation of myosin and filamentous actin interaction by tropomyosin is a central feature of contractile events in muscle and nonmuscle cells. However, little is known about molecular interactions within the complex and the trajectory of tropomyosin movement between its "open" and "closed" positions on the actin filament. Here, we report the 8 Å resolution structure of the rigor (nucleotide-free) actin-tropomyosin-myosin complex determined by cryo-electron microscopy. The pseudoatomic model of the complex, obtained from fitting crystal structures into the map, defines the large interface involving two adjacent actin monomers and one tropomyosin pseudorepeat per myosin contact. Severe forms of hereditary myopathies are linked to mutations that critically perturb this interface. Myosin binding results in a 23 Å shift of tropomyosin along actin. Complex domain motions occur in myosin, but not in actin. Based on our results, we propose a structural model for the tropomyosin-dependent modulation of myosin binding to actin.
原肌球蛋白调节肌球蛋白和丝状肌动蛋白的相互作用是肌肉和非肌肉细胞收缩活动的核心特征。然而，对于该复合物内部的分子相互作用以及原肌球蛋白在肌动蛋白丝上“开放”和“关闭”位置之间的运动轨迹知之甚少。在这里，我们通过低温电子显微镜报告了 8Å分辨率的僵硬（无核苷酸）肌动球蛋白-原肌球蛋白-肌球蛋白复合物的结构。从该映射中拟合晶体结构得到的复合物的伪原子模型定义了涉及两个相邻肌动蛋白单体和一个肌球蛋白接触的每个原肌球蛋白重复的大界面。遗传性肌病的严重形式与严重破坏该界面的突变有关。肌球蛋白结合导致原肌球蛋白沿肌动蛋白移动 23Å。肌球蛋白发生复合结构域运动，但肌动蛋白没有。基于我们的结果，我们提出了一个结构模型，用于原肌球蛋白依赖调节肌球蛋白与肌动蛋白的结合。
