Structure of the major antigenic loop of foot‐and‐mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg‐Gly‐Asp motif in the interaction.

The crystal structure of a synthetic peptide representing the major antigenic loop of foot‐and‐mouth disease virus (FMDV), complexed with the Fab fragment of a neutralizing monoclonal antibody raised against the virus, has been determined at 2.8 A resolution. The peptide shows a high degree of internal structure with a nearly cyclic conformation. The conserved Arg‐Gly‐Asp motif, involved in the viral attachment of aphtoviruses to cells, participates directly in the interaction with several complementarity determining regions of the antibody molecule. The Arg‐Gly‐Asp triplet shows the same open turn conformation found in the reduced form of FMDV of another serotype and also in integrin binding proteins. The observed interactions provide a molecular interpretation of the amino acid replacements observed to occur in mutants resistant to neutralization by this antibody. The structure also suggests a number of restrictions to variation within the epitope which are imposed to keep the Arg‐Gly‐Asp motif in its functional conformation.