Insights into the mechanism of HIV-1 envelope induced membrane fusion as revealed by its inhibitory peptides

Avraham Ashkenazi, Yechiel Shai

Research output: Contribution to journalReview articlepeer-review

Abstract

HIV-1 fusion with its target cells is mediated by the glycoprotein 41 (gp41) transmembrane subunit of the viral envelope glycoprotein (ENV). The current models propose that gp41 undergoes several conformational changes between the apposing viral and cell membranes to facilitate fusion. In this review we focus on the progress that has been made in revealing the dynamic role of the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) regions within gp41 to the fusion process. The involvement of these regions in the formation of the gp41 pre-hairpin and hairpin conformations during an ongoing fusion event was mainly discovered by their derived inhibitory peptides. For example, the core structure within the hairpin conformation in a dynamic fusion event is suggested to be larger than its high resolution structure and its minimal boundaries were determined in situ. Also, inhibitory peptides helped reveal the dual contribution of the NHR to the fusion process. Finally, we will also discuss several developments in peptide design that has led to a deeper understanding of the mechanism of viral membrane fusion.

Original languageAmerican English
Pages (from-to)349-357
Number of pages9
JournalEuropean Biophysics Journal
Volume40
Issue number4
DOIs
StatePublished - 1 Apr 2011
Externally publishedYes

Keywords

  • HIV-1 entry inhibitor
  • Membrane fusion
  • Peptide-membrane interaction
  • Viral envelope protein

All Science Journal Classification (ASJC) codes

  • Biophysics

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