Electric potentiation, cooperativity, and synergism of magainin peptides in protein-free liposomes

Abstract

Magainins, positively charged peptides present in the skin of Xenopus laevis, are known to permeabilize free-energy transducing membranes. Structural studies in otherwise protein-free model systems show alpha-helical magainins parallel to the membrane water interface. However, functional studies in biological membranes suggest that magainins operate as oligomeric complexes. Here we investigate whether magainins function as oligomers in protein-free liposomes also. We report that they do 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 transmembrane electric potential, negative inside, enhanced the activity of the 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 magainins spanning the membrane.

Energy, control and DNA structure in the living cell

“…One possible resolution of this would be that in proteinaceous membranes magainins form a complex, whereas in protein-free membranes they do not [71].…”

“…In liposomes constituted by zwitterionic and acidic phospholipids, Vaz Gomes et al [71] observed that magainin-induced membrane permeability did exhibit positive cooperativity.…”

“…Vaz Gomes et al [71] observed that, synergism between magainin 2 and PGLa (1:l) occurred also in a system devoid of a transmembrane electric potential (as opposed to other model systems). Synergism seemed also to be potentiated by increasing amounts of negative membrane charge, i.e., at higher mole fractions of DCP (dicetylphosphate).…”

“…Vaz Gomes et al [71] also investigated how a transmembrane electric potential, negative inside, affected the activity of the peptides. They concluded that electric potentials near and across the target membrane affect the activity of magainins and that the more active magainin forms are oligomers.…”

“…In view of the investigations of Vaz Gomes et al [71] and considering the physicochemical properties of magainins, the following tentative mechanism of action is proposed. Magainins are known to acquire an o-helical conformation in a hydrophobic/membrane environment.…”