BINDING OF ACYLATED PEPTIDES AND FATTY-ACIDS TO PHOSPHOLIPID-VESICLES - PERTINENCE TO MYRISTOYLATED PROTEINS

We studied the binding of fatty acids and acylated peptides to phospholipid vesicles by making electrophoretic mobility and equilibrium dialysis measurements. The binding energies of the anionic form of the fatty acids and the corresponding acylated glycines were identical; the energies increased by 0.8 kcal/mol per number of carbons in the acyl chain (N(carbon) = 10, 12, 14, 16), a value identical to that for the classical entropy-driven hydrophobic effect discussed by Tanford [The Hydrophobic Effect (1980) Wiley, New York]. The unitary Gibbs free binding energy, DELTAG(u)o, of myristoylated glycine, 8 kcal/mol, is independent of the nature of the electrically neutral lipids used to form the vesicles. Similar binding energies were obtained with other myristoylated peptides (e.g., Gly-Ala, Gly-Ala-Ala). The 8 kcal/mol, which corresponds to an effective dissociation constant of 10(-4) M for myristoylated peptides with lipids, provides barely enough energy to attach a myristoylated protein in the cytoplasm to the plasma membrane. Thus, other factors that reduce (e.g., hydrophobic interaction of myristate with the covalently attached protein) or enhance (e.g., electrostatic interactions of basic residues with acidic lipids; protein-protein interactions with intrinsic receptor proteins) the interaction of myristoylated proteins with membranes are likely to be important and may cause reversible translocation of these proteins to the membrane. Finally, our results suggest that the mass-dependent entropy price paid by a molecule when it binds to a membrane and loses one translational and two rotational degrees of freedom is small: the membrane binding energy we measure for the neutral form of myristic acid, 12 kcal/mol, agrees with the value predicted from Tanford's measurements of the partitioning of the neutral form of fatty acids between water and a bulk organic phase (14 x 0.825 = 12 kcal/mol).