Crystal structure of a neutralizing human IGG against HIV-1: a template for vaccine design

Science. 2001 Aug 10;293(5532):1155-9. doi: 10.1126/science.1061692.


We present the crystal structure at 2.7 angstrom resolution of the human antibody IgG1 b12. Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1 (HIV-1) gp120 and is one of only two known antibodies against gp120 capable of broad and potent neutralization of primary HIV-1 isolates. A key feature of the antibody-combining site is the protruding, finger-like long CDR H3 that can penetrate the recessed CD4-binding site of gp120. A docking model of b12 and gp120 reveals severe structural constraints that explain the extraordinary challenge in eliciting effective neutralizing antibodies similar to b12. The structure, together with mutagenesis studies, provides a rationale for the extensive cross-reactivity of b12 and a valuable framework for the design of HIV-1 vaccines capable of eliciting b12-like activity.

Publication types

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

MeSH terms

  • AIDS Vaccines
  • Amino Acid Sequence
  • Binding Sites
  • Binding Sites, Antibody
  • CD4 Antigens / metabolism
  • Complementarity Determining Regions / chemistry
  • Crystallography, X-Ray
  • Epitopes
  • HIV Antibodies / chemistry*
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / immunology*
  • Humans
  • Hydrogen Bonding
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / immunology
  • Models, Molecular
  • Molecular Sequence Data
  • Neutralization Tests
  • Peptide Library
  • Protein Conformation
  • Protein Structure, Tertiary
  • Templates, Genetic
  • Thermodynamics


  • AIDS Vaccines
  • CD4 Antigens
  • Complementarity Determining Regions
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin G
  • Peptide Library

Associated data

  • PDB/1HZH