Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D

Structure. 2004 Feb;12(2):193-204. doi: 10.1016/j.str.2004.01.003.


447-52D is a human monoclonal antibody isolated from a heterohybridoma derived from an HIV-1-infected individual. This antibody recognizes the hypervariable gp120 V3 loop, and neutralizes both X4 and R5 primary isolates, making it one of the most effective anti-V3 antibodies characterized to date. The crystal structure of the 447-52D Fab in complex with a 16-mer V3 peptide at 2.5 A resolution reveals that the peptide beta hairpin forms a three-stranded mixed beta sheet with complementarity determining region (CDR) H3, with most of the V3 side chains exposed to solvent. Sequence specificity is conferred through interaction of the type-II turn (residues GPGR) at the apex of the V3 hairpin with the base of CDR H3. This novel mode of peptide-antibody recognition enables the antibody to bind to many different V3 sequences where only the GPxR core epitope is absolutely required.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Crystallography
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / immunology
  • HIV-1 / chemistry*
  • HIV-1 / immunology
  • Immunoglobulin Fab Fragments / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular*
  • Neutralization Tests


  • HIV Envelope Protein gp120
  • Immunoglobulin Fab Fragments

Associated data

  • PDB/1Q1J