CRYSTALLOGRAPHIC ANALYSIS OF ANTI-P24 (HIV-1) MONOCLONAL-ANTIBODY CROSS-REACTIVITY AND POLYSPECIFICITY

The X-ray crystal structures of an anti-p24 (HIV-1) monoclonal antibod y Fab fragment alone and in complexes with the epitope peptide GATPQDL NTnL (n = norleucine), an epitope-homologous peptide GATPED LNQKLAGN, as well as two unrelated peptides GLYEW GGARITNTD and efslkGpIIqwrsG ( D-peptide), are presented to a maximum resolution of 2.6 Angstrom. The latter three peptides were identified from screening synthetic combin atorial peptide libraries. Although all peptides bind to the same anti gen combining site, the nonhomologous peptides adopt different binding conformations and also form their critical contacts with different an tibody residues. Only small readjustments are observed within the fram ework of the Fab fragment upon binding.