magainin-2-peptide--xenopus and dicetylphosphate

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.

Topics: Amino Acid Sequence; Animals; Antimicrobial Cationic Peptides; Cell Membrane Permeability; Drug Synergism; Electrochemistry; Hydrogen-Ion Concentration; Liposomes; Macromolecular Substances; Magainins; Membrane Potentials; Mitochondria, Liver; Molecular Sequence Data; Organophosphates; Peptides; Phosphatidylcholines; Phospholipids; Potassium; Rats; Spectrometry, Fluorescence; Xenopus laevis; Xenopus Proteins