Vol.49,No.6,2022
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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".
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