Tropomyosin, best known for its role in the steric regulation of muscle contraction, polymerizes head-to-tail to form cables localized along the length of both muscle and non-muscle actin-based thin filaments. In skeletal and cardiac muscles, tropomyosin, under the control of troponin and myosin, moves in a cooperative manner between blocked, closed and open positions on filaments, thereby masking and exposing actin-binding sites necessary for myosin crossbridge head interactions. While the coiled-coil signature of tropomyosin appears to be simple, closer inspection reveals surprising structural complexity required to perform its role in steric regulation. For example, component α-helices of coiled coils are typically zippered together along a continuous core hydrophobic stripe. Tropomyosin, however, contains a number of anomalous, functionally controversial, core amino acid residues. We argue that the atypical residues at this interface, including clusters of alanines and a charged aspartate, are required for preshaping tropomyosin to readily fit to the surface of the actin filament, but do so without compromising tropomyosin rigidity once the filament is assembled. Indeed, persistence length measurements of tropomyosin are characteristic of a semi-rigid cable, in this case conducive to cooperative movement on thin filaments. In addition, we also maintain that tropomyosin displays largely unrecognized and residue-specific torsional variance, which is involved in optimizing contacts between actin and tropomyosin on the assembled thin filament. Corresponding twist-induced stiffness may also enhance cooperative translocation of tropomyosin across actin filaments. We conclude that anomalous core residues of tropomyosin facilitate thin filament regulatory behavior in a multifaceted way.

中文翻译：

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原肌球蛋白结合肌动蛋白丝的新方法：细丝功能，组装和生物力学的观点。

肌球蛋白因其在肌肉收缩的空间调节中的作用而闻名，它从头到尾聚合形成沿肌肉和非肌动蛋白基细丝的长度定位的电缆。在骨骼肌和心肌中，原肌球蛋白在肌钙蛋白和肌球蛋白的控制下以协同方式在细丝的封闭，闭合和开放位置之间移动，从而掩盖和暴露肌球蛋白横桥头相互作用所必需的肌动蛋白结合位点。尽管原肌球蛋白的卷曲螺旋特征看起来很简单，但仔细检查后发现，执行其在空间调节中的作用需要令人惊讶的结构复杂性。例如，盘绕的线圈的组分α-螺旋通常沿着连续的芯疏水条被拉链在一起。然而，Tropomyosin包含许多异常现象，在功能上有争议的核心氨基酸残基。我们认为该界面的非典型残基（包括丙氨酸簇和带电荷的天冬氨酸）是预成型原肌球蛋白以使其易于适应肌动蛋白丝表面所需的，但这样做不会损害原肌球蛋白在纤维丝组装后的刚性。实际上，原肌球蛋白的持续长度测量是半刚性电缆的特征，在这种情况下有利于细丝上的协同运动。此外，我们还认为原肌球蛋白在很大程度上显示出无法识别的残基特异性扭转变异，这涉及优化组装的细丝上肌动蛋白与原肌球蛋白之间的接触。相应的扭曲诱发的刚度也可能增强原肌球蛋白跨肌动蛋白丝的协同移位。