ROLE OF PRENYLATION IN THE INTERACTION OF THE A-FACTOR MATING PHEROMONE WITH PHOSPHOLIPID-BILAYERS

We have studied the interaction between phospholipids and a-factor (YI IKGVFWDPAC-[Farn]OMe), S-alkylated forms of a-factor with the farnesyl group substituted by methyl, hexadecanyl, or benzyl groups, and trunc ated forms of this lipopeptide. Circular dichroism studies suggest tha t, despite its lack of farnesylation, S-methyl-a-factor is incorporate d into vesicles of dimyristoylphosphatidylcholine in a conformation si milar to that which a-factor adopts in this membrane. However, studies of the intrinsic fluorescence of the Trp residues of these peptides i ndicate that this residue is more deeply imbedded into the bilayer in the case of the farnesylated peptide. The a-factor is more effective i n raising the bilayer to the hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine than is the S-methyl-a-factor. Thi s bilayer-stabilizing ability is also reflected in a-factor inhibiting leakage from vesicles of N-methyldioleoylphosphatidylethanolamine. St udies on a-factor analogs permit the conclusion that the bilayer-stabi lizing effect of a-factor is not solely a consequence of its greater p artitioning into the membrane but is also a consequence of the degree of penetration into the bilayer and the specific conformation of the p eptide at the membrane interface. These results indicate that the farn esyl group alone, in the absence of cellular factors, bestows a partic ular physical interaction with membranes.