Structural properties of the putative fusion peptide of fertilin, a protein active in sperm-egg fusion, upon interaction with the lipid bilayer

We recently demonstrated that a peptide representing the putative fusion do main of fertilin, a surface membrane protein of sperm involved in sperm-egg fusion, induces fusion of large unilamellar vesicles containing negatively charged lipids [Martin, I., and Ruysschaert, J, M. (1997) FEES Lett. 405, 351-355], In the present work, we demonstrate that increasing the concentra tion in negatively charged lipids strongly enhances the binding of the fert ilin fusion peptide to the membrane, suggesting that electrostatic attracti ons play a crucial role in the binding process. While no significant change of the secondary structure content is observed by increasing the amounts o f negatively charged lipids in the bilayer, the orientation of the alpha-he lix changes from a parallel to an oblique orientation in the membrane. This topological change is confirmed by amide II hydrogen/deuterium exchange me asurements that monitor the accessibility of the peptide to the water mediu m. Differential scanning calorimetry data also suggest that the fertilin fu sion peptide lowers the bilayer to hexagonal phase transition temperature o f model membranes composed of mixtures of dipalmitoleoylphosphatidylethanol amine and 1-palmitoyl-2-oleoylphosphatidylserine and therefore promotes neg ative curvature in Lipid vesicles. A comparison of the biophysical properti es and the membrane-perturbing activities of fertilin and of viral fusion p eptides is discussed in terms of sperm-egg fusion and virus cell fusion.