Crystal structure of a human immunodeficiency virus type 1 neutralizing antibody, 50.1, in complex with its V3 loop peptide antigen

Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6325-9. doi: 10.1073/pnas.90.13.6325.

Abstract

The crystal structure of the Fab fragment of a human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibody Fab has been determined at 2.8 A resolution in complex with a linear 16-residue peptide from the third hypervariable region (V3) of gp120. The first 9 residues of the peptide are ordered in the electron density maps, and their conformation is in partial agreement with the beta-strand-type II beta-turn structure predicted for this portion of the V3 loop. Notably, several of the peptide residues that are well conserved among different HIV-1 isolates contact a nonpolar 25-A-long groove in the antibody-combining site. The largely extended structure of the peptide differs from the beta-turns seen as the primary determinants in other published anti-peptide Fab structures. Analysis of the specific Fab-peptide interactions only partially explains the MN isolate specificity shown by this antibody.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Computer Graphics
  • Crystallization
  • HIV Antibodies / chemistry*
  • HIV Envelope Protein gp120 / chemistry*
  • HIV-1 / immunology*
  • Immunoglobulin Fab Fragments / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Protein Conformation
  • X-Ray Diffraction

Substances

  • Antibodies, Monoclonal
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Immunoglobulin Fab Fragments
  • Peptide Fragments