T细胞受体
糖基化
聚糖
分子动力学
化学
动力学
氢键
分子
生物物理学
T细胞
生物
糖蛋白
免疫系统
生物化学
免疫学
计算化学
物理
量子力学
有机化学
作者
Zachary A. Rollins,Bradley Harris,Steven C. George,Roland Faller
标识
DOI:10.1080/07391102.2022.2091660
摘要
The binding interaction between the T-cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) is modulated by several factors (known and unknown), however, investigations into effects of glycosylation are limited. A fully glycosylated computational model of the TCR bound to the pMHC is developed to investigate the effects of glycosylation on dissociation kinetics from the pMHC. Here, we examine the effects of N-glycosylation on TCR-pMHC bond strength using steered molecular dynamic simulations. N-glycosylation is a post-translational modification that adds sugar moieties to molecules and can modulate the activity of several immune molecules. Using a TCR-pMHC pair found in melanoma as a case study, our study demonstrates that N-glycosylation of the TCR-pMHC alters the proteins’ conformation; increases the bond lifetime; and increases the number of hydrogen bonds and Lennard-Jones Contacts involved in the TCR-pMHC bond. We find that weak glycan-protein or glycan-glycan interactions impact the equilibrated structure of the TCR and pMHC leading to an increase in the overall bond strength of the TCR-pMHC complex including the duration and energetic strength under constant load. These results indicate that N-glycosylation plays an important role in the TCR-pMHC bond and should be considered in future computational and experimental studies.Communicated by Ramaswamy H. Sarma
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