The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence.
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 alpha-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 alpha-helical conformation by this gp41 region might be functionally meaningful.
Suárez
T
T
Unidad de Biofisica, Departamento de Bioquimica, Universidaad del Pais Vasco, Aptdo, 644, 48080, Bilboa, Spain.
Nir
S
S
Goñi
F M
FM
Saéz-Cirión
A
A
Nieva
J L
JL
D000595:Amino Acid Sequence; D001665:Binding Sites; D002784:Cholesterol / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared
D015700:HIV Envelope Protein gp41; D008081:Liposomes; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine