Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.
Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.
Curr Opin Immunol. 2021 Jun;70:82-89. doi: 10.1016/j.coi.2021.04.004. Epub 2021 May 13.
The peptide binding site of major histocompatibility complex (MHC) class I molecules is natively unfolded when devoid of peptides. Peptide binding stabilizes the structure and slows the dynamics, but peptide-specific and subtype-specific motions influence, and are influenced by, interaction with assembly chaperones, the T cell receptor, and other class I-binding proteins. The molecular mechanisms of cooperation between peptide, class I heavy chain, and beta-2 microglobulin are insufficiently known but are being elucidated by nuclear magnetic resonance and other modern methods. It appears that micropolymorphic clusters of charged amino acids, often hidden in the molecule interior, determine the dynamics and thus chaperone dependence, cellular fate, and disease association of class I.
主要组织相容性复合体（MHC）I 类分子的肽结合位点在没有肽时天然处于无规卷曲状态。肽结合稳定了结构并减缓了动力学，但肽特异性和亚型特异性运动影响并受与组装伴侣、T 细胞受体和其他 I 类结合蛋白的相互作用的影响。肽、I 类重链和β2-微球蛋白之间合作的分子机制了解不足，但通过核磁共振和其他现代方法正在阐明。似乎带电氨基酸的微多态簇，通常隐藏在分子内部，决定了 I 类分子的动力学，从而决定了伴侣的依赖性、细胞命运和疾病相关性。
