Insights into the mechanism of HIV-1 envelope induced membrane fusion as revealed by its inhibitory peptides.
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.
The Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Avraham
A
Ashkenazi
Yechiel
Y
Shai
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000494:pharmacology*
D019380:Anti-HIV Agents; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D014759:Viral Envelope Proteins
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