A multiply substituted G–H loop from foot-and-mouth disease virus in complex with a neutralizing antibody: a role for water molecules

摘要: The crystal structure of a 15 amino acid synthetic peptide, corresponding to the sequence major antigenic site A (G–H loop VP1) from multiple variant foot-and-mouth disease virus (FMDV), has been determined at 2·3 A resolution. peptide includes four substitutions in relative previously studied representing FMDV C-S8c1 and corresponds natural isolate subtype C1. was complexed with Fab fragment neutralizing monoclonal antibody 4C4. adopts compact fold nearly cyclic conformation disposition receptor-recognition motif Arg–Gly–Asp that is closely related for viral loop, as part virion, unsubstituted antigen bound antibodies. New structural findings include observation well-defined solvent molecules appear play role stabilizing its interactions antibody. Structural results are supported by molecular-dynamic simulations. multiply substituted developed compensatory mechanisms bind very similar counterpart. One water molecule, which steric reasons could not occupy same position antigen, establishes hydrogen bonds three acids. constancy an domain despite implications vaccine design.