结晶学
主要组织相容性复合体
人类白细胞抗原
沟槽(工程)
蛋白质结构
抗原
侧链
分子置换
表位
组织相容性
次要组织相容性抗原
立体化学
化学
MHC I级
生物
晶体结构
遗传学
生物化学
材料科学
冶金
聚合物
有机化学
作者
Mark A. Saper,Pamela J. Bjorkman,Don C. Wiley
标识
DOI:10.1016/0022-2836(91)90567-p
摘要
The three-dimensional structure of the human histocompatibility antigen HLA-A2 was determined at 3.5 A resolution by a combination of isomorphous replacement and iterative real-space averaging of two crystal forms. The monoclinic crystal form has now been refined by least-squares methods to an R-factor of 0.169 for data from 6 to 2.6 A resolution. A superposition of the structurally similar domains found in the heterodimer, alpha 1 onto alpha 2 and alpha 3 onto beta 2m, as well as the latter pair onto the ancestrally related immunoglobulin constant domain, reveals that differences are mainly in the turn regions. Structural features of the alpha 1 and alpha 2 domains, such as conserved salt-bridges that contribute to stability, specific loops that form contacts with other domains, and the antigen-binding groove formed from two adjacent helical regions on top of an eight-stranded beta-sheet, are analyzed. The interfaces between the domains, especially those between beta 2m and the HLA heavy chain presumably involved in beta 2m exchange and heterodimer assembly, are described in detail. A detailed examination of the binding groove confirms that the solvent-accessible amino acid side-chains that are most polymorphic in mouse and human alleles fill up the central and widest portion of the binding groove, while conserved side-chains are clustered at the narrower ends of the groove. Six pockets or sub-sites in the antigen-binding groove, of diverse shape and composition, appear suited for binding side-chains from antigenic peptides. Three pockets contain predominantly non-polar atoms; but others, especially those at the extreme ends of the groove, have clusters of polar atoms in close proximity to the "extra" electron density in the binding site. A possible role for beta 2m in stabilizing permissible peptide complexes during folding and assembly is presented.
科研通智能强力驱动
Strongly Powered by AbleSci AI