Temperature-dependent intermediates in HIV-1 envelope glycoprotein-mediated fusion revealed by inhibitors that target N- and C-terminal helical regions of HIV-1 gp41

Biochemistry. 2004 Jun 29;43(25):8230-3. doi: 10.1021/bi049957v.

Abstract

Peptides derived from the N- (N-HR) and C- (C-HR) terminal heptad repeat regions adjacent to the fusion peptide and transmembrane domains, respectively, of human immunodeficiency virus (HIV)-1 gp41 inhibit HIV-1 viral envelope glycoproteins (Env)-mediated cell fusion specifically. The mechanism of HIV-1 Env-mediated cell fusion and its inhibition by agents that target the N- and C-HR regions was investigated. Priming experiments with Env-expressing cells indicate that the N-HR region but not the C-HR region is exposed by treatment with sCD4 at 31 degrees C, whereas both the N- and C-HR regions are exposed at 37 degrees C.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / metabolism*
  • HIV Fusion Inhibitors / pharmacology*
  • HIV-1 / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Fusion / drug effects
  • Mice
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Peptide Fragments / pharmacology*
  • Protein Structure, Secondary
  • Receptors, CXCR4 / metabolism
  • Temperature

Substances

  • CD4 Antigens
  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Peptide Fragments
  • Receptors, CXCR4