CRYSTAL-STRUCTURE OF A HUMAN RHINOVIRUS NEUTRALIZING ANTIBODY COMPLEXED WITH A PEPTIDE DERIVED FROM VIRAL CAPSID PROTEIN VP2

The three-dimensional structure of the complex between the Fab fragmen t of an anti-human rhinovirus neutralizing antibody (8F5) and a cross- reactive synthetic peptide from the viral capsid protein VP2 has been determined at 2.5 Angstrom resolution by crystallographic methods. The refinement is presently at an R factor of 0.18 and the antigen-bindin g site and viral peptide are well defined. The peptide antigen adopts a compact fold by two tight turns and interacts through hydrogen bonds , some with ionic character, and van der Waals contacts with antibody residues from the six hypervariable loops as well as several framework amino acids. The conformation adopted by the peptide is closely relat ed to the corresponding region of the viral protein VP2 on the surface of human rhinovirus 1A whose three-dimensional structure is known. Im plications for the cross-reactivity between peptides and the viral cap sid are discussed. The peptide-antibody interactions, together with th e analysis of mutant viruses that escape neutralization by 8F5 suggest two different mechanisms for viral escape. The comparison between the complexed and uncomplexed antibody structures shows important conform ational rearrangements, especially in the hypervariable loops of the h eavy chain. Thus, it constitutes a clear example of the 'induced fit' molecular recognition mechanism.