Interaction of HIV-1 gp41 core with NPF motif in Epsin: implication in endocytosis of HIV

J Biol Chem. 2008 May 30;283(22):14994-5002. doi: 10.1074/jbc.M800525200. Epub 2008 Mar 28.


The human immunodeficiency virus, type 1 (HIV-1), gp41 core plays an important role in fusion between viral and target cell membranes. We previously identified an HIV-1 gp41 core-binding motif HXXNPF (where X is any amino acid residue). In this study, we found that Asn, Pro, and Phe were the key residues for gp41 core binding. There are two NPF motifs in Epsin-1-(470-499), a fragment of Epsin, which is an essential accessory factor of endocytosis that can dock to the plasma membrane by interacting with the lipid. Epsin-1-(470-499) bound significantly to the gp41 core formed by the polypeptide N36(L8)C34 and interacted with the recombinant soluble gp41 containing the core structure. A synthetic peptide containing the Epsin-1-(470-499) sequence could effectively block entry of HIV-1 virions into SupT1 T cells via the endocytosis pathway. These results suggest that interaction between Epsin and the gp41 core, which may be present in the target cell membrane, is probably essential for endocytosis of HIV-1, an alternative pathway of HIV-1 entry into the target cell.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Amino Acid Motifs / genetics
  • Cell Line
  • Endocytosis / drug effects*
  • HIV Envelope Protein gp41 / antagonists & inhibitors*
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / metabolism
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Humans
  • Membrane Lipids / genetics
  • Membrane Lipids / metabolism
  • Peptides / genetics
  • Peptides / pharmacology*
  • Virus Internalization / drug effects*


  • Adaptor Proteins, Vesicular Transport
  • HIV Envelope Protein gp41
  • Membrane Lipids
  • Peptides
  • epsin
  • gp41 protein, Human immunodeficiency virus 1