MODULATION OF LIPID POLYMORPHISM BY THE FELINE LEUKEMIA-VIRUS FUSION PEPTIDE - IMPLICATIONS FOR THE FUSION MECHANISM

The structural effects of the fusion peptide of feline leukemia virus (FeLV) on lipid polymorphism were studied, using differential scanning calorimetry (DSC, P-31 nuclear magnetic resonance (NMR), and time-res olved X-ray diffraction. This peptide lowers the bilayer to inverted h exagonal phase transition temperature, T-H, Of dipalmitoleoylphosphati dylethanolamine (DiPoPE) at peptide mole fractions of up to 1.5 x 10(- 3) at pH 5.0 and at pH 7.4. The temperature at which isotropic P-31 NM R signals for monomethyldioleoylphosphatidylethanolamine (MeDOPE) firs t occurred is lowered by the FeLV peptide. The amount of isotropic sig nal seen at 40 degrees C is directly correlated to the peptide:lipid m olar ratio. In the peptide-containing samples, more lipid remains in t he isotropic state over the whole recorded temperature range. Isotropi c P-31 NMR signals were observed for DiPoPE in the presence of the FeL V peptide for the entire recorded temperature range of 35-50 degrees C , while pure DiPoPE showed no significant amount of isotropic signal. X-ray studies of DiPoPE show the formation of a new lipid phase with p eptide, which is not seen in the pure Lipid samples. Disordering of th e L-alpha phase is evidenced by broadening of the diffraction peaks, a nd the hexagonal cell parameter is decreased with peptide present. Our results suggest that the FeLV peptide is increasing the negative curv ature of the lipid system, which is thought to be crucial to the forma tion of highly bent, high-energy structural fusion intermediates, such as the ''stalk'' model. Fusion activity for this putative fusogenic p eptide was also demonstrated, using a resonance energy transfer (RET) Lipid mixing assay. To our knowledge, this work provides the first pub lished experimental evidence of both fusogenic activity and effects on Lipid polymorphism for the FeLV fusion peptide.