Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody Academic Article uri icon

Overview

MeSH Major

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • HIV-1
  • Viral Fusion Proteins

abstract

  • The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.

authors

publication date

  • May 13, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4917739

Digital Object Identifier (DOI)

  • 10.1126/science.aae0474

PubMed ID

  • 27174988

Additional Document Info

start page

  • 828

end page

  • 33

volume

  • 352

number

  • 6287