Interactions of Protein Antigens with Antibodies

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-01, Vol.93 (1), p.7-12
• Main Authors: Davies, David R., Cohen, Gerson H.
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Antibodies; Antibodies, Anti-Idiotypic - chemistry; Antibodies, Anti-Idiotypic - immunology; Antibodies, Monoclonal - chemistry; Antigen-Antibody Reactions; Antigens; Antigens, Viral - chemistry; Antigens, Viral - immunology; Atoms; Bacterial Proteins; Binding sites; Binding Sites, Antibody; Chemistry; Chickens; Epitope Mapping; Epitopes; Epitopes - chemistry; Hydrogen bonds; Immunoglobulin Fab Fragments - chemistry; Mice; Models, Molecular; Molecular biology; Molecules; Muramidase - chemistry; Muramidase - immunology; Neuraminidase - chemistry; Neuraminidase - immunology; Orthomyxoviridae Infections - enzymology; Orthomyxoviridae Infections - immunology; Phosphoenolpyruvate Sugar Phosphotransferase System - chemistry; Phosphoenolpyruvate Sugar Phosphotransferase System - immunology; Protein Binding; Protein Conformation; Proteins; Review; Structure-Activity Relationship; Surface areas; Viruses; X-Ray Diffraction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.1.7

There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other protein-protein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogenbond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding. For the most studied antigen, lysozyme, the epitopes for four antibodies occupy ≈ 45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens.