[Molecular action mechanisms and membrane recognition of membrane-acting antimicrobial peptides].
A number of antimicrobial peptides have been isolated in the animal kingdom, serving as defensive or offensive weapons. The mechanisms of their action are considered to be the permeability of bacterial membranes, although the details are not yet clarified. I have studied the interactions of several antibiotic peptides with both artificial lipid bilayers and biomembranes to elucidate the molecular mechanisms of the action and to find out the rationale for their membrane specificity. Magainin 2 from the Xenopus skin was found to form a peptide-lipid supramolecular complex pore in the membrane, followed by peptide internalization, simultaneously dissipating the transmembrane potential and the lipid asymmetry. This novel mechanism also works for a wasp bee venom, mastoparan X. Tachyplesin I from Tachypleus and a bee venom, melittin, also translocate across the membrane by forming a pore. The membrane selectivity of these peptides is closely related to their affinity for the lipids constituting the membrane surface. A strategy for developing a potent antibiotic was discussed based on these results.
Matsuzaki
K
K
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D006737:Horseshoe Crabs; D036341:Intercellular Signaling Peptides and Proteins; D054806:Magainins; D008555:Melitten / Q000493:pharmacokinetics / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology; D014863:Wasps; D014981:Xenopus; D029867:Xenopus Proteins
D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D054806:Magainins; D008563:Membrane Lipids; D010455:Peptides; D010456:Peptides, Cyclic; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C057636:tachyplesin peptide, Tachypleus tridentatus; D008555:Melitten; C071123:mastoparan X