Crystallographic analysis of anti-p24 (HIV-1) monoclonal antibody cross-reactivity and polyspecificity

Cell. 1997 Dec 12;91(6):811-20. doi: 10.1016/s0092-8674(00)80469-9.

Abstract

The X-ray crystal structures of an anti-p24 (HIV-1) monoclonal antibody Fab fragment alone and in complexes with the epitope peptide GATPQDLNTnL (n = norleucine), an epitope-homologous peptide GATPEDLNQKLAGN, as well as two unrelated peptides GLYEWGGARITNTD and efslkGpllqwrsG (D-peptide), are presented to a maximum resolution of 2.6 A. The latter three peptides were identified from screening synthetic combinatorial peptide libraries. Although all peptides bind to the same antigen combining site, the nonhomologous peptides adopt different binding conformations and also form their critical contacts with different antibody residues. Only small readjustments are observed within the framework of the Fab fragment upon binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Cross Reactions
  • Crystallography, X-Ray
  • Epitopes / chemistry
  • Epitopes / immunology
  • HIV Core Protein p24 / chemistry*
  • HIV Core Protein p24 / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Light Chains / chemistry
  • Immunoglobulin Variable Region / chemistry
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Library*
  • Protein Conformation*
  • Structure-Activity Relationship

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • HIV Core Protein p24
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Peptide Library