SPECIFICITY POCKETS FOR THE SIDE-CHAINS OF PEPTIDE ANTIGENS IN HLA-AW68
SPECIFICITY POCKETS FOR THE SIDE-CHAINS OF PEPTIDE ANTIGENS IN HLA-AW68
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DOI：
10.1038/342692a0
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发表时间：
1989-12-07
期刊：
影响因子：
64.8
通讯作者：
WILEY, DC
中科院分区：
文献类型：
--
作者：
GARRETT, TPJ;SAPER, MA;WILEY, DC
我们用X射线晶体学方法测定了第二种人类组织相容性糖蛋白HLA-Aw 68的结构，并将其分辨率提高到2.6 μ m。总的来说，该结构与HLA-A2的结构极其相似（参考文献1，2;和M.A.S.et al.，尽管抗原结合裂缝2中多态残基3，4处的11个氨基酸取代改变了该位点的详细形状和静电荷，但这一点仍有待进一步研究。在α1-结构域的α-螺旋下方延伸的裂缝内的一个显著的带负电荷的口袋，为识别带正电荷的侧链或肽N末端提供了一个潜在的亚位点。未解释的电子密度，推测代表未知的“抗原”，其似乎与HLA-A2结构1中所见的不同，占据裂缝并延伸到HLA-Aw 68中的带负电荷的口袋中。HLA-Aw 68和HLA-A2的结构展示了多态性如何产生和改变定位为结合肽侧链的亚位点（口袋），从而表明了外来抗原结合中等位基因特异性的结构基础。
WE have determined the structure of a second human histocompati-bility glycoprotein, HLA-Aw68, by X-ray crystallography and refined it to a resolution of 2.6 Å. Overall, the structure is extremely similar to that of HLA-A2 (refs 1, 2; and M.A.S.et al., manuscript in preparation), although the 11 amino-acid substitutions at polymorphic residues3,4in the antigen-binding cleft2alter the detailed shape and electrostatic charge of that site. A prominent negatively charged pocket within the cleft extends underneath the α-helix of the α1-domain, providing a potential subsite for recognizing a positively charged side chain or peptide N terminus. Uninterpreted electron density, presumably representing an unknown 'antigen(s)', which seems to be different from that seen in the HLA-A2 structure1, occupies the cleft and extends into the negatively charged pocket in HLA-Aw68. The structures of HLA-Aw68 and HLA-A2 demonstrate how polymorphism creates and alters subsites (pockets) positioned to bind peptide side chains, thereby suggesting the structural basis for allelic specificity in foreign antigen binding.