Magainins as paradigm for the mode of action of pore forming polypeptides.
Magainins are a class of antimicrobial peptides discovered in the skin of Xenopus laevis. The peptides kill bacteria by permeabilizing the cell membranes without exhibiting significant toxicity against mammalian cells, and are a promising candidate for a new antibiotic of therapeutic value. The main target of the peptides are considered to be the lipid matrix of the membranes. This review summarizes studies on magainin-lipid interactions in comparison with other pore forming peptides. The selective toxicity can be at least partly explained by preferential interactions of magainins with anionic phospholipids abundant in bacterial membranes. A novel mode of action is discussed in detail, i.e., the formation of a dynamic peptide-lipid supramolecular pore, which allows the mutually coupled transbilayer transport of ions, lipids, and peptides per se.
Matsuzaki
K
K
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. katsumim@pharm.kyoto-u.ac.jp
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D002463:Cell Membrane Permeability / Q000187:drug effects*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D054806:Magainins; D008563:Membrane Lipids / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D029867:Xenopus Proteins
D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D054806:Magainins; D008563:Membrane Lipids; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C053300:magainin 1 peptide, Xenopus