Interactions of the HIV-1 fusion peptide with large unilamellar vesicles and monolayers. A cryo-TEM and spectroscopic study.
We have examined the interaction of the human immunodeficiency virustype 1 fusion peptide (23 amino acid residues) and of a Trp-containing analog with vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol (molar ratio, 1:1:1). Both the native and the Trp-substituted peptides bound the vesicles to the same extent and induced intervesicular lipid mixing with comparable efficiency. Infrared reflection-absorption spectroscopy data are compatible with the adoption by the peptide of a main beta-sheet structure in a cospread lipid/peptide monolayer. Cryo-transmission electron microscopy observations of peptide-treated vesicles reveal the existence of a peculiar morphology consisting of membrane tubular elongations protruding from single vesicles. Tryptophan fluorescence quenching by brominated phospholipids and by water-soluble acrylamide further indicated that the peptide penetrated into the acyl chain region closer to the interface rather than into the bilayer core. We conclude that the differential partition and shallow penetration of the fusion peptide into the outer monolayer of a surface-constrained bilayer may account for the detected morphological effects. Such single monolayer-restricted interaction and its structural consequences are compatible with specific predictions of current theories on viral fusion.
Agirre
A
A
Unidad de Biofisica (CSIC-EHU/UPV) y Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain.
Flach
C
C
Goñi
F M
FM
Mendelsohn
R
R
Valpuesta
J M
JM
Wu
F
F
Nieva
J L
JL
D020106:Acrylamide; D020285:Cryoelectron Microscopy; D015497:HIV-1; D008051:Lipid Bilayers / Q000737:chemistry; D008567:Membranes, Artificial; D008854:Microscopy, Electron; D010539:Permeability; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared / Q000379:methods; D013499:Surface Properties; D014760:Viral Fusion Proteins / Q000737:chemistry*
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D014760:Viral Fusion Proteins; D020106:Acrylamide