Identification of the HIV-1 gp41 core-binding motif--HXXNPF

FEBS Lett. 2006 Sep 4;580(20):4807-14. doi: 10.1016/j.febslet.2006.07.067. Epub 2006 Aug 4.

Abstract

The HIV-1 gp41 core, a six-helix bundle formed between the N- and C-terminal heptad repeats, plays a critical role in fusion between the viral and target cell membranes. Using N36(L8)C34 as a model of the gp41 core to screen phage display peptide libraries, we identified a common motif, HXXNPF (X is any of the 20 natural amino acid residues). A selected positive phage clone L7.8 specifically bound to N36(L8)C34 and this binding could be blocked by a gp41 core-specific monoclonal antibody (NC-1). JCH-4, a peptide containing HXXNPF motif, effectively inhibited HIV-1 envelope glycoprotein-mediated syncytium-formation. The epitope of JCH-4 was proven to be linear and might locate in the NHR regions of the gp41 core. These data suggest that HXXNPF motif may be a gp41 core-binding sequence and HXXNPF motif-containing molecules can be used as probes for studying the role of the HIV-1 gp41 core in membrane fusion process.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Amino Acid Motifs*
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Epitopes
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / genetics*
  • HIV Envelope Protein gp41 / metabolism
  • Humans
  • Membrane Fusion
  • Mice
  • Peptide Library
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Protein Structure, Secondary*

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • HIV Envelope Protein gp41
  • Peptide Library
  • Peptides