2022年第49卷第6期目录
|
|
封面故事:TCR-CD3跨膜蛋白复合物在适应性免疫应答、胞内外信号的传递中起着重要作用。因
此TCR-CD3复合物的自组装分子机制对于T细胞受体的免疫疗法发展具有重要的意义。由于实验技
术手段对于跨膜蛋白研究存在局限性,不能很好地展现跨膜蛋白原子水平的信息以及微妙级别的
实时观测和分析。王凤丽等用分子动力学模拟的方法对TCR-CD3复合物的自组装进行了研究,发
现仅含跨膜区的TCR-CD3复合物不足以介导各亚基间的自组装,ζζ'的胞外区在TCR-CD3复合物自
组装过程中的重要性。自组装过程中存在着αβ依次结合δε'、γε、ζζ'的组装顺序,α第253位的精氨
酸突变为亮氨酸会降低α第258位的赖氨酸与δε'跨膜区天冬氨酸的相互作用,并且CD3共受体中δε'
在稳定TCR-CD3复合物跨膜区相互作用的过程中占据着核心地位。
(王凤丽,陈佳林,何程智,罗施中. TCR-CD3复合物跨膜区自组装的分子机制,本期第1094-1102页)
Cover Story:Objective The T cell receptor-co-receptor complex (TCR-CD3) plays an important role in the adaptive immune response, and the interaction between its subunits has always been a research hotspot. Due to the limitations of traditional experiments, the study of transmembrane protein TCR-CD3 complexes cannot go deep into the microscopic level.Methods Therefore, we used molecular dynamics simulation methods to analyze the self-assembly mechanism of TCR-CD3 complexes.Results Through coarse-grained simulation (CGMD), we found that the TCR-CD3 complex has an assembly sequence in which αβ sequentially binds δε", γε, and ζζ" during the assembly process, and explained that the αR253 mutation reduces the interaction between αK258 and δε".Conclusion We demonstrated that only the transmembrane region of the TCR-CD3 complex is not sufficient to mediate the specific interaction between the subunits of the TCR-CD3 complex. The results of steered dynamics (SMD) and all-atom simulation (AAMD) indicate that the extracellular interaction between ζζ" and the rest of TCR-CD3 is stronger than the transmembrane region. The absence of ζζ" makes the stability of αβδε"γε little change, while the absence of δε" greatly reduces the stability of αβγεζζ".
|
学者与科研
综述与专论
研究快报
研究报告
技术与方法
|
|