COMPARISON OF THE P2 SPECIFICITY POCKET IN 3 HUMAN HISTOCOMPATIBILITY ANTIGENS - HLA-A-ASTERISK-6801, HLA-A-ASTERISK-0201, AND HLA-B-ASTERISK-2705
COMPARISON OF THE P2 SPECIFICITY POCKET IN 3 HUMAN HISTOCOMPATIBILITY ANTIGENS - HLA-A-ASTERISK-6801, HLA-A-ASTERISK-0201, AND HLA-B-ASTERISK-2705
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DOI：
10.1073/pnas.90.17.8053
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发表时间：
1993-09-01
影响因子：
11.1
通讯作者：
WILEY, DC
中科院分区：
文献类型：
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作者：
GUO, HC;MADDEN, DR;WILEY, DC
对HLA-A*6801、HLA-A*0201和HLA-B*2705的x射线结构坐标进行分析，以检验它们在肽结合中的选择性基础。在这三种HLA亚型中，结合肽的第二个氨基酸残基（P2残基）侧链的口袋分别显示出对Val、Leu和Arg的偏好。HLA-B*2705的arg特异性口袋与HLA-A*0201和HLA-A*6801明显不同，这是由于形成口袋表面的侧链存在许多差异。HLA-A*0201和HLA-A*6801特异性差异的原因更为微妙，既取决于口袋残基Val-67构象的变化，也取决于残基9的序列差异。Val-67构象变化似乎是由α - 1结构域α -螺旋相对于β -片的位置变化引起的，实际上可能取决于远离P2口袋的氨基添加差异。通过对P2侧链与其结合袋相互作用的立体化学分析，可以估计其对肽结合自由能变化的贡献。
Coordinates from x-ray structures of HLA-A*6801, HLA-A*0201, and HLA-B*2705 were analyzed to examine the basis for their selectivity in peptide binding. The pocket that binds the side chain of the peptide's second amino acid residue (P2 residue) shows a preference for Val, Leu, and Arg in these three HLA subtypes, respectively. The Arg-specific pocket of HLA-B*2705 differs markedly from those of HLA-A*0201 and HLA-A*6801, as a result of numerous differences in the side chains that form the pocket's surface. The cause of the specificity differences between HLA-A*0201 and HLA-A*6801 is more subtle and depends both on a change in conformation of pocket residue Val-67 and on a sequence difference at residue 9. The Val-67 conformational change appears to be caused by a shift in the position of the alpha1-domain alpha-helix relative to the beta-sheet in the cleft and may, in fact, depend on amino add differences remote from the P2 pocket. Analysis of the stereochemistry of the P2 side chain interacting with its binding pocket permits an estimate to be made of its contribution to the free-energy change of peptide binding.