Antibacterial activity and pore-forming properties of ceratotoxins: a mechanism of action based on the barrel stave model.
Ceratotoxins are alpha-helical cationic peptides isolated from the medfly Ceratitis capitata. These amphipathic peptides were found to display strong antibacterial activity and weak hemolytic activity. When reconstituted into planar lipid bilayers, ceratotoxins developed highly asymmetric I/V curves under voltage ramps and formed, in single-channel experiments, well-defined voltage-dependent ion channels according to the barrel stave model. The antibacterial activity and pore-forming properties of these molecules were well correlated. Similar experiments performed with synthesized truncated fragments showed that the C-terminal domain of ceratotoxins is strongly implicated in the formation of helical bundles in the membrane whereas the largely cationic N-terminal region is likely to anchor ceratotoxins on the lipid surface.
Bessin
Yannick
Y
CBS, UMR 5048 CNRS, UMR 554 INSERM, Université de Montpellier 1, 29 rue de Navacelles, 34090 Montpellier, France.
Saint
Nathalie
N
Marri
Laura
L
Marchini
Daniela
D
Molle
Gérard
G
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D033622:Ceratitis capitata / Q000737:chemistry; D004553:Electric Conductivity; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D029941:Fish Proteins; D006460:Hemolysin Proteins / Q000494:pharmacology; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D007473:Ion Channels / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry
D000900:Anti-Bacterial Agents; D029941:Fish Proteins; D006460:Hemolysin Proteins; D019476:Insect Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D011506:Proteins; C082689:ceratotoxin A protein, Ceratitis capitata; C105851:pleurocidin