title: 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.
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.
authors.affiliation: Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Gallo
authors.forename: G Marius
authors.initials: GM
authors.lastname: Clore
authors.forename: John M
authors.initials: JM
authors.lastname: Louis
authors.forename: Carole A
authors.initials: CA
authors.lastname: Bewley
authors.forename: Robert
authors.initials: R
authors.lastname: Blumenthal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D019718:Receptors, CXCR4 / Q000378:metabolism; D013696:Temperature
chemical_list: D015704:CD4 Antigens; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D019718:Receptors, CXCR4