Membrane orientation of the SIV fusion peptide determines its effect on bilayer stability and ability to promote membrane fusion.
The amino terminal segment of the gp32 glycoprotein of SIV has been identified as an important region for membrane fusion. A synthetic dodecapeptide corresponding to this amino terminal segment, SIVwt, can promote the fusion of liposomes. This peptide inserts at an oblique angle into the membrane. If the amino acid sequence of this peptide is changed, while maintaining the same amino acid composition, the resulting peptide, SIVmutV, no longer promotes fusion and it is oriented perpendicular to the plane of the bilayer. In the present work we demonstrate that SIVwt, but not SIVmutV, can lower the bilayer to hexagonal phase transition temperature of model membranes composed of dipalmitoleoyl phosphatidylethanolamine. In addition the SIVwt promotes the formation of structures which give rise to isotropic 31P NMR signals in mixtures with monomethyldioleoyl phosphatidylethanolamine. These structures are not formed with SIVmutV and their formation with SIVwt is suppressed with lysophosphatidylcholine. Taken together these results suggest that the observed correlation between oblique insertion of viral fusion peptides into membranes and their fusogenicity may be a consequence on these peptides increasing negative monolayer curvature.
Epand
R F
RF
Department of Biochemistry, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Martin
I
I
Ruysschaert
J M
JM
Epand
R M
RM
D000595:Amino Acid Sequence; D002152:Calorimetry, Differential Scanning; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion / Q000502:physiology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013816:Thermodynamics; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D015686:Gene Products, env; D008051:Lipid Bilayers; D008081:Liposomes; D010446:Peptide Fragments; D015682:Retroviridae Proteins, Oncogenic; D014760:Viral Fusion Proteins; C059580:transmembrane protein, Simian immunodeficiency virus