Orientation and structure of the NH2-terminal HIV-1 gp41 peptide in fused and aggregated liposomes.
For several retroviruses, the N-terminal hydrophobic sequence of the viral envelope glycoprotein has been shown to play a crucial role in the interaction between the virus and the host cell membrane. We report here on the interaction of a synthetic 16 residues peptide corresponding to the gp41 NH2-terminal sequence of Human Immunodeficiency Virus with the phospholipid bilayer. Fluorescence energy transfer measurements show that this peptide can induce lipid mixing of large unilamellar vesicles (LUV) of various compositions at pH 7.4 and 37 degrees C. LUV undergo fusion, provided they contained phosphatidylethanolamine (PE) in their lipid composition. To provide insight into the mechanism of the fusion event, the peptide secondary structure and orientation in the lipid bilayer were determined using Fourier Transform Infrared Spectroscopy (FTIR). The peptide adopts mainly a beta-sheet conformation in the absence of lipids. After interaction with LUV the beta-sheet is partly converted into alpha-helix. The orientation of the peptide with respect to the lipid acyl chains depends on the presence of PE in the lipid bilayer. The peptide is inserted into the lipid bilayer with the helix axis oriented parallel to the lipid acyl chains in the fused vesicles, whereas it is adsorbed parallel to the lipid/water interface in the aggregated vesicles. The role of the two kinds of orientation during the fusion event is discussed.
Martin
I
I
Laboratoire de Chimie-Physique des Macromolécules aux Interfaces CP206/2, Université Libre de Bruxelles, Belgium.
Defrise-Quertain
F
F
Decroly
E
E
Vandenbranden
M
M
Brasseur
R
R
Ruysschaert
J M
JM
D000595:Amino Acid Sequence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure
D015700:HIV Envelope Protein gp41; D008081:Liposomes