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, dioieoylphosphatidyletha nolamine and cholesterol (molar ratio, 1:1:1). Both the native and the Trp- substituted peptides bound the vesicles to the same extent and induced inte rvesicular lipid mixing with comparable efficiency. Infrared reflection-abs orption spectroscopy data are compatible with the adoption by the peptide o f a main P-sheet structure in a cospread lipid/peptide monolayer. Cryo-tran smission electron microscopy observations of peptide-treated vesicles revea l the existence of a peculiar morphology consisting of membrane tubular elo ngations protruding from single vesicles. Tryptophan fluorescence quenching by brominated phospholipids and by water-soluble acrylamide further indica ted that the peptide penetrated into the acyl chain region closer to the in terface rather than into the bilayer core. We conclude that the differentia l partition and shallow penetration of the fusion peptide into the outer mo nolayer of a surface-constrained bilayer may account for the detected morph ological effects. Such single monolayer-restricted interaction and its stru ctural consequences are compatible with specific predictions of current the ories on viral fusion. (C) 2000 Elsevier Science B.V. All rights reserved.