Recently, our understanding of the structural basis of troponin-tropomyosin's Ca2+-triggered regulation of striated muscle contraction has advanced greatly, particularly via cryo-EM data. Compelling atomic models of troponin-tropomyosin-actin were published, for both apo- and Ca2+-saturated states of the cardiac thin filament. Subsequent electron microscopy and computational analyses have supported and further elaborated the findings. Per cryo-EM, each troponin is highly extended, and contacts both tropomyosin strands, which lie on opposite sides of the actin filament. In the apo-state characteristic of relaxed muscle, troponin and tropomyosin hinder strong myosin-actin binding in several different ways, apparently barricading the actin more substantially than does tropomyosin alone. The troponin core domain, the C-terminal third of TnI, and tropomyosin under the influence of a 64-residue helix of TnT located at overlap of adjacent tropomyosins, all are in positions that would hinder strong myosin binding to actin. In the Ca2+-saturated state, the TnI C-terminus dissociates from actin and binds in part to TnC; the core domain pivots significantly; the N-lobe of TnC binds specifically to actin and tropomyosin; and tropomyosin rotates partially away from myosin's binding site on actin. At the overlap domain, Ca2+ causes much less tropomyosin movement, so a more inhibitory orientation persists. In the myosin-saturated state of the thin filament, there is a large additional shift in tropomyosin, with molecular interactions now identified between tropomyosin and both actin and myosin. A new era has arrived for investigation of the thin filament, and for functional understandings that increasingly accommodate the recent structural results.

中文翻译：

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肌钙蛋白揭示了横纹肌中细丝开关的结构

最近，我们对肌钙蛋白-原肌球蛋白的 Ca2+ 触发的横纹肌收缩调节的结构基础的理解有了很大进展，特别是通过冷冻电镜数据。发表了令人信服的肌钙蛋白-原肌球蛋白-肌动蛋白原子模型，用于心脏细丝的载脂蛋白和 Ca2+ 饱和状态。随后的电子显微镜和计算分析支持并进一步阐述了这些发现。根据冷冻电镜，每个肌钙蛋白都高度延伸，并接触位于肌动蛋白丝相对两侧的原肌球蛋白链。在肌肉松弛的脱基状态特征中，肌钙蛋白和原肌球蛋白以几种不同的方式阻碍肌球蛋白-肌动蛋白的强结合，显然比单独的原肌球蛋白更明显地阻碍肌动蛋白。肌钙蛋白核心结构域，TnI 的 C 端三分之一，和原肌球蛋白在位于相邻原肌球蛋白重叠处的 TnT 的 64 个残基螺旋的影响下，都处于阻碍强肌球蛋白与肌动蛋白结合的位置。在 Ca2+ 饱和状态下，TnI C 末端与肌动蛋白分离并部分与 TnC 结合；核心领域显着转变；TnC 的 N 瓣与肌动蛋白和原肌球蛋白特异性结合；并且原肌球蛋白部分旋转远离肌动蛋白上的肌球蛋白结合位点。在重叠域，Ca2+ 引起的原肌球蛋白运动要少得多，因此仍然存在更多的抑制方向。在细丝的肌球蛋白饱和状态下，原肌球蛋白发生了很大的额外变化，现在确定了原肌球蛋白与肌动蛋白和肌球蛋白之间的分子相互作用。细丝研究的新时代已经到来，