Convergent solutions to binding at a protein-protein interface
Convergent solutions to binding at a protein-protein interface
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DOI：
10.1126/science.287.5456.1279
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发表时间：
2000-02-18
期刊：
影响因子：
56.9
通讯作者：
Wells, JA
中科院分区：
文献类型：
--
作者：
DeLano, WL;Ultsch, MH;Wells, JA
人免疫球蛋白G的Fe片段上的铰链区与在C-H2和C-H3结构域之间的共同位点结合的至少四种不同的天然蛋白质支架相互作用。该“共有”位点对于通过噬菌体展示在体外选择的高亲和力（解离常数，约25纳摩尔）的随机肽的结合也是占优势的。因此，该位点由于其固有的生理化学性质而不是单独的生物学功能似乎是优选的。与Fc复合的所选13-氨基酸肽的2.7埃晶体结构表明，该肽采用与其他Fc结合蛋白完全不同的紧凑结构。然而，肽的特异性Fc结合相互作用强烈模拟其他蛋白质的相互作用。可用的Fc-复合物晶体结构的并置显示会聚结合表面是高度可接近的、自适应的和疏水的，并且包含相对较少的用于极性相互作用的位点。这些都是可以促进交叉反应性结合的性质，这对于蛋白质-蛋白质相互作用，特别是蛋白质-受体复合物是常见的。
The hinge region on the Fe fragment of human immunoglobulin G interacts with at least four different natural protein scaffolds that bind at a common site between the C-H2 and C-H3 domains. This "consensus" site was also dominant for binding of random peptides selected in vitro for high affinity (dissociation constant, about 25 nanomolar) by bacteriophage display, Thus, this site appears to be preferred owing to its intrinsic physiochemical properties, and not for biological function alone. A 2.7 angstrom crystal structure of a selected 13-amino acid peptide in complex with Fc demonstrated that the peptide adopts a compact structure radically different from that of the other Fc binding proteins. Nevertheless, the specific Fc binding interactions of the peptide strongly mimic those of the other proteins. Juxtaposition of the available Fc-complex crystal structures showed that the convergent binding surface is highly accessible, adaptive, and hydrophobic and contains relatively few sites for polar interactions. These are all properties that may promote cross-reactive binding, which is common to protein-protein interactions and especially hormone-receptor complexes.