Antibody-antigen interactions: Contact analysis and binding site topography
Antibody-antigen interactions: Contact analysis and binding site topography
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DOI：
10.1006/jmbi.1996.0548
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发表时间：
1996-10-11
影响因子：
5.6
通讯作者：
Thornton, JM
中科院分区：
文献类型：
--
作者：
MacCallum, RM;Martin, ACR;Thornton, JM
我们分析了抗体 Fv 和 Fab 晶体结构中的抗原接触残基和结合位点形状，现已从蛋白质数据库中获取。呈现每个抗体残基的抗原接触倾向，允许基于观察到的抗原接触提出互补决定区（CDR）的新定义，接触在位于结合位点中央的CDR残基处更常见；一些不太中心的CDR残基仅与大抗原接触。 CDR 内的非接触残基与 Chothia 及其同事鉴定的对定义“规范”构象很重要的残基一致。已经开发出一种通过总体形貌对蛋白质表面进行分类的客观方法，并将其应用于抗体结合位点表面。表面被分为四个拓扑类别：凹面和中凹面（主要是半抗原结合剂）、脊状（主要是肽结合剂）和平面（主要是蛋白质结合剂）。我们已经确定了十对复合和非复合抗体-抗原晶体结构的拓扑类别；四个改变络合的拓扑类别。结果将用于抗体工程、抗原对接和临床免疫学。为了演示一种应用，我们展示了如何使用数据来定位抗体结构上的抗原结合袋。 (C) 1996 学术出版社有限公司
We have analysed antigen-contacting residues and combining site shape in the antibody Fv and Fab cry-stal structures now available from the Protein Data Bank. Antigen-contacting propensities are presented for each antibody residue, allowing a new definition for the complementarity determining regions (CDRs) to be proposed based on observed antigen contacts, Contacts are more common at CDR residues which are located centrally within the combining site; some less central CDR residues are only contacted by large antigens. Non-contacting residues within the CDRs coincide with residues identified by Chothia and co-workers as important in defining ''canonical'' conformations.An objective means of classifying protein surfaces by gross topography has been developed and applied to the antibody combining site surfaces. The surfaces have been clustered into four topographic classes: concave and moderately concave (mostly hapten binders), ridged (mostly peptide binders) and planar (mostly protein binders). We have determined the topographic classes fur ten pairs of complexed and uncomplexed antibody-antigen crystal structures; four change topographic class on complexation.The results will be of use in antibody engineering, antigen docking and in clinical immunology. To demonstrate one application, we show how the data can be used to locate the antigen binding pocket on antibody structures. (C) 1996 Academic Press Limited