We investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) - CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al. (2019). We find that the TCR extracellular (EC) domain is highly variable in its orientation by attaining tilt angles relative to the membrane normal that range from 15° to 55°. The tilt angle of the TCR EC domain is both coupled to a rotation of the domain and to characteristic changes throughout the TCR - CD3 complex, in particular in the EC interactions of the C_ FG loop of the TCR, as well as in the orientation of transmembrane helices. The concerted motions of the membrane-embedded TCR - CD3 complex revealed in our simulations provide atomistic insights on conformational changes of the complex in response to tilt-inducing forces on antigen-bound TCRs.

中文翻译：

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T 细胞受体 CD3 复合物的结构变异和协同运动


我们基于Dong 等人最近确定的冷冻电镜结构，在广泛的原子分子动力学模拟中研究了膜嵌入 T 细胞受体 (TCR) - CD3 复合物的结构和方向变异性。 （2019） 。我们发现，TCR 胞外 (EC) 结构域的方向高度可变，相对于膜法线的倾斜角度范围为 15° 至 55°。 TCR EC 结构域的倾斜角既与结构域的旋转有关，又与整个 TCR-CD3 复合物的特征变化有关，特别是在 TCR 的 C_FG 环的 EC 相互作用中，以及与跨膜螺旋。我们的模拟中揭示的膜嵌入 TCR-CD3 复合物的协同运动提供了复合物构象变化的原子学见解，以响应抗原结合 TCR 上的倾斜诱导力。