TCR-CD3复合物跨膜区自组装的分子机制  

The Molecular Mechanism of TCR-CD3 Complex Self-assembly

作　　者：王凤丽 陈佳林 何程智 罗施中[1] WANG Feng-Li;CHEN Jia-Lin;HE Cheng-Zhi;LUO Shi-Zhong(Beijing Advanced Innovation Center for Soft Matter Science and Engineering,College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029,China)

机构地区：[1]北京化工大学生命科学与技术学院北京软物质科学与工程高精尖创新中心,北京100029

出　　处：《生物化学与生物物理进展》2022年第6期1094-1102,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(22077010,11902023);天津大学精密测试技术及仪器国家重点实验室开放课题(pilab1902)资助项目。

摘　　要：目的T细胞受体-共受体复合物(TCR-CD3)在适应性免疫应答中起着重要作用,其亚基间的相互作用一直是研究热点。由于传统实验的局限性,对于跨膜蛋白TCR-CD3复合物的研究不能深入到微观层面。方法利用分子动力学模拟方法(包括粗粒化模拟、拉伸动力学、全原子模拟)分析TCR-CD3复合物的自组装机制。结果通过粗粒化模拟(CGMD)发现,TCR-CD3复合物在组装过程中存在着αβ依次结合δε’、γε、ζζ’的组装顺序,并阐述了α;突变会降低α;与δε’的相互作用。结论本文论证了仅存在TCR-CD3复合物的跨膜区不足以介导TCR-CD3复合物亚基间的特异性相互作用。拉伸动力学(SMD)和全原子模拟(AAMD)的结果说明,ζζ’与TCR-CD3其余部分之间的胞外区相互作用强于跨膜区,同时ζζ’的缺失对αβδε’γε的稳定性影响最小,而δε’的缺失对αβγεζζ’的稳定性影响最大。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 whichαβsequentially bindsδε’,γε,andζζ’during the assembly process,and explained that theα;mutation reduces the interaction betweenα;andδε’.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 betweenζζ’and the rest of TCR-CD3 is stronger than the transmembrane region.The absence ofζζ’makes the stability ofαβδε’γεlittle change,while the absence ofδε’greatly reduces the stability ofαβγεζζ’.

关 键 词：TCR-CD3复合物 粗粒化模拟 全原子模拟 拉伸动力学模拟 跨膜蛋白 

分 类 号：Q6[生物学—生物物理学] R9[医药卫生—药学]