Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria.
Institute of Information and Communication Technologies (IICT), Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Block 25A, 1113 Sofia, Bulgaria.
Cells. 2019 Jul 13;8(7):720. doi: 10.3390/cells8070720.
The interaction of antigenic peptides (p) and major histocompatibility complexes (pMHC) with T-cell receptors (TCR) is one of the most important steps during the immune response. Here we present a molecular dynamics simulation study of bound and unbound TCR and pMHC proteins of the LC13-HLA-B*44:05-pEEYLQAFTY complex to monitor differences in relative orientations and movements of domains between bound and unbound states of TCR-pMHC. We generated local coordinate systems for MHC α1- and MHC α2-helices and the variable T-cell receptor regions TCR V and TCR V and monitored changes in the distances and mutual orientations of these domains. In comparison to unbound states, we found decreased inter-domain movements in the simulations of bound states. Moreover, increased conformational flexibility was observed for the MHC α2-helix, the peptide, and for the complementary determining regions of the TCR in TCR-unbound states as compared to TCR-bound states.
抗原肽 (p) 与主要组织相容性复合物 (pMHC) 与 T 细胞受体 (TCR) 的相互作用是免疫反应过程中的最重要步骤之一。在这里，我们对 LC13-HLA-B*44:05-pEEYLQAFTY 复合物的结合和未结合的 TCR 和 pMHC 蛋白进行了分子动力学模拟研究，以监测 TCR-pMHC 结合和未结合状态下各结构域的相对取向和运动的差异。我们为 MHC α1-和 MHC α2-螺旋以及 TCR 的可变 T 细胞受体区 TCR V 和 TCR V 生成了局部坐标系，并监测了这些结构域之间的距离和相互取向的变化。与未结合状态相比，我们发现结合状态模拟中各结构域之间的运动减少。此外，与 TCR 结合状态相比，在 TCR 未结合状态下 MHC α2-螺旋、肽和 TCR 的互补决定区的构象灵活性增加。
