Molecular basis for membrane selectivity of an antimicrobial peptide, magainin 2.
Magainin peptides, isolated from Xenopus skin, kill bacteria by permeabilizing their cell membranes whereas they do not lyse erythrocytes. To elucidate the rationale for this membrane selectivity, we compared the effects of the membrane lipid composition and the transmembrane potential on the membrane-lytic power of magainin 2 with that of hemolytic melittin. The activity of magainin to zwitterionic phospholipids constituting the erythrocyte surface was extremely weak compared with that of melittin, and acidic phospholipids are necessary for effective action. The presence of sterols reduced the susceptibility of the membrane to magainin. The generation of an inside-negative transmembrane potential enhanced magainin-induced hemolysis. We can conclude that the absence of any acidic phospholipids on the outer monolayer and the abundant presence of cholesterol, combined with the lack of the transmembrane potential, contribute to the protection of erythrocytes from magainin's attack.
Matsuzaki
K
K
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Sugishita
K
K
Fujii
N
N
Miyajima
K
K
D000408:Alamethicin / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects; D006096:Gramicidin / Q000737:chemistry / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D054806:Magainins; D008555:Melitten / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D008563:Membrane Lipids / Q000737:chemistry; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry; D012794:Sialic Acids / Q000737:chemistry; D013261:Sterols / Q000737:chemistry; D029867:Xenopus Proteins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D054806:Magainins; D008563:Membrane Lipids; D010456:Peptides, Cyclic; D010743:Phospholipids; D012794:Sialic Acids; D013261:Sterols; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C057636:tachyplesin peptide, Tachypleus tridentatus; D006096:Gramicidin; D008555:Melitten; D000408:Alamethicin