RELATIONSHIP OF MEMBRANE CURVATURE TO THE FORMATION OF PORES BY MAGAININ-2

Magainin 2, an antimicrobial peptide from the Xenopus skin, kills bact eria by permeabilizing the cell membranes. We have proposed that the p eptide preferentially interacts with acidic phospholipids to form a pe ptide-lipid supramolecular complex pore, which allows mutually coupled transbilayer traffic of ions, lipids, and peptides, thus simultaneous ly dissipating transmembrane potential and lipid asymmetry [Matsuzaki, K., Murase, O., Fujii, N., and Miyajima, K. (1996) Biochemistry 35, 1 1361-11368]. In this paper, we examined the effect of membrane curvatu re strain on pore formation. Magainin effectively forms the pore only in phosphatidylglycerol bilayers at low peptide-to-lipid ratios, well below 1/100. In contrast, the permeabilization of phosphatidylserine, phosphatidic acid, or cardiolipin bilayers occurred at much higher pep tide-to-lipid ratios (1/50 to 1/10) with some morphological change of the vesicles. The latter three classes of phospholipids are known to f orm hexagonal II structures under conditions of reduced interlipid ele ctrostatic repulsions. Incorporation of phosphatidylethanolamine also inhibited the magainin-induced pore formation in the inhibitory order of dioleoylphosphatidylethanolamine > dielaidoylphosphatidylethanolami ne. Addition of a small amount of palmitoyllysophosphatidylcholine enh anced the peptide-induced permeabilization of phosphatidylglycerol bil ayers. Magainin greatly raised the bilayer to hexagonal II phase trans ition temperature of dipalmitoleoylphosphatidylethanolamine. These res ults suggest that the peptide imposes positive curvature strain, facil itating the formation of a torus-type pore, and that the presence of n egative curvature-inducing lipids inhibits pore formation.