期刊
PROTEIN ENGINEERING DESIGN & SELECTION
卷 17, 期 5, 页码 463-472出版社
OXFORD UNIV PRESS
DOI: 10.1093/protein/gzh058
关键词
antibody-antigen complex; antibody-hapten complex; immunoglobulin superfamily; molecular recognition
资金
- NIGMS NIH HHS [R01 GM 46535] Funding Source: Medline
In this paper, we present the association requirements across a wide variety of antibody-antigen complexes. Phylogenetic analysis clearly indicates the representative nature of our structural dataset. Antigen molecules range from small-molecule haptens to complete protein structures. Common association motifs identified include five conserved tyrosine residues and a single conserved arginine residue from CDR-H3. Further, specificity is refined by a diverse array of antibody-antigen electrostatic interactions that maximize complex specificity. Through analysis of calculated pK(a) shifts on antigen binding, we find that these interactions are conserved at 23 alignment 'hot-spot' positions. Despite consistent roles in defining substrate specificity, 16 hot-spot positions are conserved less than 50% of the time. On the other hand, because of the conserved functional role of these positions, mutant screening at hot-spots is more likely to result in increased antigen specificity than elsewhere. Therefore, we believe these results should facilitate subsequent antibody design experimentation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据