Structure of an HIV gp120 Envelope Glycoprotein in Complex With the CD4 Receptor and a Neutralizing Human Antibody

Nature. 1998 Jun 18;393(6686):648-59. doi: 10.1038/31405.

Abstract

The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4 Antigens / chemistry*
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray
  • Glycosylation
  • HIV Antibodies / chemistry*
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / immunology
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp41 / metabolism
  • Humans
  • Immunoglobulin Fragments / chemistry
  • Immunoglobulin Fragments / immunology
  • Membrane Fusion
  • Models, Molecular
  • Molecular Sequence Data
  • Neutralization Tests
  • Protein Conformation
  • Receptors, CCR5 / metabolism

Substances

  • CD4 Antigens
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Immunoglobulin Fragments
  • Receptors, CCR5

Associated data

  • PDB/1GC1