ELECTRIC POTENTIATION, COOPERATIVITY, AND SYNERGISM OF MAGAININ PEPTIDES IN PROTEIN-FREE LIPOSOMES

Magainins, positively charged peptides present in the skin of Xenopus laevis, are known to permeabilize free-energy transducing membranes. S tructural studies in otherwise protein-free model systems show alpha-h elical magainins parallel to the membrane water interface. However, fu nctional studies in biological membranes suggest that magainins operat e as oligomeric complexes. Here we investigate whether magainins funct ion as oligomers in protein-free liposomes also. We report that they d o exhibit strong positive heterocooperativity. The magainins, magainin 2 and PGLa, act synergistically. Both activity and cooperativity are enhanced by net negative charge of the liposomal membranes. A transmem brane electric potential, negative inside, enhanced the activity of th e peptides. We propose a model in which (i) binding to the surface of the membrane, mainly guided by electrostatic interactions, occurs and (ii) the bound form is in equilibrium with an n-meric complex of magai nins spanning the membrane.