Ikemizu S, Sparks L M, van der Merwe P A, Harlos K, Stuart D I, Jones E Y, Davis S J
Laboratory of Molecular Biophysics, the Rex Richards Building, South Parks Road, Oxford, OX1 3QU, United Kingdom.
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4289-94. doi: 10.1073/pnas.96.8.4289.
The binding of the cell surface molecule CD58 (formerly lymphocyte function-associated antigen 3) to its ligand, CD2, significantly increases the sensitivity of antigen recognition by T cells. This was the first heterophilic cell adhesion interaction to be discovered and is now an important paradigm for analyzing the structural basis of cell-cell recognition. The crystal structure of a CD2-binding chimeric form of CD58, solved to 1.8-A resolution, reveals that the ligand binding domain of CD58 has the expected Ig superfamily V-set topology and shares several of the hitherto unique structural features of CD2, consistent with previous speculation that the genes encoding these molecules arose via duplication of a common precursor. Nevertheless, evidence for considerable divergence of CD2 and CD58 is also implicit in the structures. Mutations that disrupt CD2 binding map to the highly acidic surface of the AGFCC'C" beta-sheet of CD58, which, unexpectedly, lacks marked shape complementarity to the equivalent, rather more basic CD58-binding face of human CD2. The specificity of the very weak interactions of proteins mediating cell-cell recognition may often derive largely from electrostatic complementarity, with shape matching at the protein-protein interface being less exact than for interactions that combine specificity with high affinity, such as those involving antibodies.
细胞表面分子CD58（以前称为淋巴细胞功能相关抗原3）与其配体CD2的结合，显著提高了T细胞对抗原识别的敏感性。这是首次发现的异嗜性细胞黏附相互作用，现在已成为分析细胞间识别结构基础的重要范例。解析到1.8埃分辨率的CD58的一种CD2结合嵌合形式的晶体结构表明，CD58的配体结合结构域具有预期的免疫球蛋白超家族V型拓扑结构，并且具有CD2迄今一些独特的结构特征，这与之前推测编码这些分子的基因是通过一个共同前体的复制产生的一致。然而，结构中也隐含着CD2和CD58存在相当大差异的证据。破坏CD2结合的突变定位到CD58的AGFCC'C"β折叠的高酸性表面，出乎意料的是，该表面与人CD2的等效且更碱性的CD58结合面缺乏明显的形状互补性。介导细胞间识别的蛋白质之间非常弱的相互作用的特异性，可能通常很大程度上源于静电互补性，蛋白质 - 蛋白质界面处的形状匹配比那些将特异性与高亲和力结合的相互作用（如涉及抗体的相互作用）要不那么精确。
