Interbilayer lipid mixing induced by the human immunodeficiency virus type-1 fusion peptide on large unilamellar vesicles: the nature of the nonlamellar intermediates.
A peptide corresponding to the 23 N-terminal amino acid residues of the human immunodeficiency virus type-1 (HIV-1) gp41 has the capacity to induce intervesicular lipid mixing in large unilamellar liposomes composed of dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE) and cholesterol (CHOL) (molar ratio, 1:1:1). Cryo-transmission electron microscopy (cryo-TEM) of diluted vesicles to which peptides has been externally added reveals a morphology that is compatible with the formation of nonlamellar lipidic aggregates during the time-course of lipid mixing. 31P-nuclear magnetic resonance and 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMADPH) steady-state anisotropy data at equilibrium indicate that the peptide is able to modulate the lipid polymorphism in pelletted membranes by: (i) promoting the thermotropic formation of inverted phases; and (ii) driving the lamellar-to-nonlamellar transition towards the formation of isotropic phases. Therefore, our combined morphological and spectroscopic data reveal the existence of a direct correlation between the ability of the externally added peptide to induce lipid-mixing in dilute liposome samples and its capacity to modulate lipid polymorphism in stacked bilayers.
Pereira
F B
FB
Unidad de Biofísica (CSIC-EHU/UPV), Universidad del País Vasco, Bilbao, Spain.
Valpuesta
J M
JM
Basañez
G
G
Goñi
F M
FM
Nieva
J L
JL
D000595:Amino Acid Sequence; D002784:Cholesterol / Q000737:chemistry; D020285:Cryoelectron Microscopy; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000648:ultrastructure; D015497:HIV-1; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*
D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C020888:1,2-dielaidoylphosphatidylethanolamine; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine