Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers

Immunity. 2014 May 15;40(5):669-80. doi: 10.1016/j.immuni.2014.04.008. Epub 2014 Apr 24.

Abstract

All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / ultrastructure
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / ultrastructure
  • Binding Sites, Antibody / immunology
  • Cell Line
  • Crystallization
  • Crystallography, X-Ray
  • Epitopes / immunology
  • HEK293 Cells
  • HIV Antibodies / immunology*
  • HIV Antibodies / ultrastructure
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp41 / immunology*
  • HIV Envelope Protein gp41 / metabolism
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1 / immunology
  • Humans
  • Molecular Sequence Data
  • Polysaccharides / immunology
  • Protein Structure, Quaternary
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Polysaccharides
  • env Gene Products, Human Immunodeficiency Virus
  • gp140 envelope protein, Human immunodeficiency virus 1
  • gp41 protein, Human immunodeficiency virus 1

Associated data

  • PDB/4NUG
  • PDB/4NUJ