Padlan E A
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Proteins. 1990;7(2):112-24. doi: 10.1002/prot.340070203.
A detailed analysis of the structural aspects of antibody-antigen interactions has been made possible by the availability of X-ray structures for three complexes of antilysozyme Fabs to lysozyme (reviewed by Davies et al.: J. Biol. Chem. 263:10541-10544, 1988.) Examination of the antigen-contacting residues in the three antilysozyme Fabs reveals the occurrence of a large number of aromatics, particularly tyrosines, and the absence of apolar, aliphatic residues. Calculation of the frequency of occurrence of the various amino acid types reveals that tyrosines are three times, and histidines and asparagines eight times, more likely to be found in the complementarity-determining regions than in the framework of the variable domains. Analysis of the solvent accessibility of the residues in Fvs (the modules containing variable domains of the light and heavy chains) of known three-dimensional structure indicates that tyrosines and tryptophans are more exposed when they occur in the complementarity-determining regions than when in the framework. Furthermore, many more of the asparagines in the complementarity-determining regions than in the framework are buried. These asparagines appear to have a structural role in that they hydrogen-bond through their side chains to other side chains and, even more so, to the protein backbone. The stabilizing effect of the asparagines, plus the rigidity of the framework, may serve to allow the greater exposure of the aromatic residues to solvent. In view of the greater potential contribution of aromatic side chains to the total binding energy, these results suggest that antibody combining sites have structural features that make them especially suited for interacting with ligands.
抗溶菌酶Fab与溶菌酶的三种复合物的X射线结构的可得性，使得对抗体 - 抗原相互作用的结构方面进行详细分析成为可能（戴维斯等人对此进行了综述：《生物化学杂志》263:10541 - 10544，1988年）。对三种抗溶菌酶Fab中与抗原接触的残基的研究表明，存在大量芳香族氨基酸，尤其是酪氨酸，并且不存在非极性脂肪族残基。对各种氨基酸类型出现频率的计算表明，在互补决定区中发现酪氨酸的可能性是可变区框架中的三倍，组氨酸和天冬酰胺是八倍。对已知三维结构的Fv片段（包含轻链和重链可变区的模块）中残基的溶剂可及性分析表明，酪氨酸和色氨酸出现在互补决定区时比在框架中时更暴露。此外，互补决定区中被埋藏的天冬酰胺比框架中的多得多。这些天冬酰胺似乎具有结构作用，因为它们通过侧链与其他侧链形成氢键，甚至更多地与蛋白质主链形成氢键。天冬酰胺的稳定作用加上框架的刚性，可能有助于使芳香族残基更多地暴露于溶剂中。鉴于芳香族侧链对总结合能的潜在贡献更大，这些结果表明抗体结合位点具有使其特别适合与配体相互作用的结构特征。
