The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence

• Published in: FEBS letters Vol. 477; no. 1; pp. 145 - 149
• Main Authors: Suárez, Tatiana, Nir, Shlomo, Goñi, Félix M., Saéz-Cirión, Asier, Nieva, José L.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.07.2000
• Subjects: AIDS/HIV; Amino Acid Sequence; ANTS, 8-aminonaphthalene-1,3,6-trisulfonic acid; Binding Sites; CHOL, cholesterol; Cholesterol - metabolism; DMSO, dimethylsulfoxide; DOPC, dioleoylphosphatidylcholine; DOPE, dioleoylphosphatidylethanolamine; DPX, p-xylenebis(pyridinium)bromide; Fusion peptide; gp41; HIV Envelope Protein gp41 - chemistry; HIV Envelope Protein gp41 - genetics; HIV Envelope Protein gp41 - metabolism; HIV Envelope Protein gp41 - pharmacology; HIV-1; HIV-1, human immunodeficiency virus type 1; HIVc, synthetic sequence (20 aa) representing residues 664–683 of HIV-1 gp160 precursor (BH10 viral isolate); Kinetics; Liposomes - chemistry; Liposomes - drug effects; Liposomes - metabolism; LUV, large unilamellar vesicles; Membrane fusion; Membrane Fusion - drug effects; Molecular Sequence Data; Mutation - genetics; N-NBD-PE, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine; N-Rh-PE, N-(lissamine rhodamine B sulfonyl) phosphatidylethanolamine; NATA, N-acetyl-L-tryptophanamide; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptide–lipid interaction; Permeability - drug effects; Phosphatidylcholines - metabolism; Phosphatidylethanolamines - metabolism; Protein Structure, Secondary; Spectrophotometry, Infrared; Viral fusion; HIV-1; Membrane fusion; Viral fusion; CHOL, cholesterol; ANTS, 8-aminonaphthalene-1,3,6-trisulfonic acid; DPX, p-xylenebis(pyridinium)bromide; N-NBD-PE, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine; NATA, N-acetyl- L-tryptophanamide; Fusion peptide; DMSO, dimethylsulfoxide; DOPE, dioleoylphosphatidylethanolamine; N-Rh-PE, N-(lissamine rhodamine B sulfonyl) phosphatidylethanolamine; gp41; Peptide–lipid interaction; HIV-1, human immunodeficiency virus type 1; DOPC, dioleoylphosphatidylcholine; LUV, large unilamellar vesicles; HIV c, synthetic sequence (20 aa) representing residues 664–683 of HIV-1 gp160 precursor (BH10 viral isolate)
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)01785-3

We have investigated membrane interactions and perturbations induced by NH 2-DKWASLWNWFNITNWLWYIK-COOH (HIV c), representing the membrane interface-partitioning region that precedes the transmembrane anchor of the human immunodeficiency virus type-1 gp41 fusion protein. The HIV c peptide bound with high affinity to electrically neutral vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol (molar ratio, 1:1:1), and induced vesicle leakage and lipid mixing. Infrared spectra suggest that these effects were promoted by membrane-associated peptides adopting an α-helical conformation. A sequence representing a defective gp41 phenotype unable to mediate both cell–cell fusion and virus entry, was equally unable to induce vesicle fusion, and adopted a non-helical conformation in the membrane. We conclude that membrane perturbation and adoption of the α-helical conformation by this gp41 region might be functionally meaningful.