Max Planck Institute of Colloids and Interfaces, Department of Theory and Bio-Systems, Potsdam, Germany.
Institute of Physics, Polish Academy of Sciences, Warsaw, Poland.
Elife. 2021 Sep 7;10:e67195. doi: 10.7554/eLife.67195.
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 Cβ 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.
我们基于 Dong 等人于 2019 年确定的最近的冷冻电镜结构，通过广泛的原子分子动力学模拟研究了膜嵌入的 T 细胞受体（TCR）-CD3 复合物的结构和取向变异性。我们发现，TCR 细胞外（EC）结构域通过相对于膜法线获得从 15°到 55°的倾斜角度，在取向方面具有高度的可变性。TCR EC 结构域的倾斜角度既与该结构域的旋转相关，也与 TCR-CD3 复合物的特征变化相关，特别是 TCR 的 Cβ FG 环的 EC 相互作用，以及跨膜螺旋的取向。我们的模拟揭示了膜嵌入的 TCR-CD3 复合物的协同运动，为复杂的构象变化提供了原子水平的见解，以响应抗原结合的 TCR 上的倾斜诱导力。
