Structural evidence for recognition of a single epitope by two distinct antibodies

• Published in: Proteins, structure, function, and bioinformatics Vol. 40; no. 4; pp. 572 - 578
• Main Authors: Fleury, Damien, Daniels, Rod S., Skehel, John J., Knossow, Marcel, Bizebard, Thierry
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.09.2000
• Subjects: Amino Acid Sequence; Antibodies - chemistry; antibody; Antigen-Antibody Complex - chemistry; Crystallography, X-Ray; epitope; Epitopes; hemagglutinin; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Immunoglobulin Fab Fragments - chemistry; influenza; Models, Molecular; Molecular Sequence Data; redundancy; structure
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/1097-0134(20000901)40:4<572::AID-PROT30>3.0.CO;2-N

The structure of a complex between the hemagglutinin of influenza virus and the Fab of a neutralizing antibody was determined by X‐ray crystallography at 2.8 Å resolution. This antibody and another which has only 56% sequence identity bind to the same epitope with very similar affinities and in the same orientation. One third of the interactions is conserved in the two complexes; a significant proportion of the interactions that differ are established by residues of the H3 complementarity‐determining regions (CDR) which adopt distinct conformations in the two antibodies. This demonstrates that there is a definite flexibility in the selection of antibodies that bind to a given epitope, despite the high affinity of their complexes. This flexibility allows the humoral immune response to be redundant, a feature that may be useful in achieving longer lasting protection against evolving viral pathogens. Proteins 2000;40:572–578. © 2000 Wiley‐Liss, Inc.