Fiche publication
Date publication
décembre 2007
Journal
Biochemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
,
Dr KICHLER Antoine
Tous les auteurs :
Mason AJ, Bertani P, Moulay G, Marquette A, Perrone B, Drake AF, Kichler A, Bechinger B
Lien Pubmed
Résumé
Chrysophsin-1 is an amphipathic alpha-helical antimicrobial peptide produced in the gill cells of red sea bream. The peptide has broad range activity against both Gram-positive and Gram-negative bacteria but is more hemolytic than other antimicrobial peptides such as magainin. Here we explore the membrane interaction of chrysophsin-1 and determine its toxicity, in vitro, for human lung fibroblasts to obtain a mechanism for its antimicrobial activity and to understand the role of the unusual C-terminal RRRH sequence. At intermediate peptide concentrations, solid-state NMR methods reveal that chrysophsin-1 is aligned parallel to the membrane surface and the lipid acyl chains in mixed model membranes are destabilized, thereby being in agreement with models where permeabilization is an effect of transient membrane disruption. The C-terminal RRRH sequence was shown to have a large effect on the insertion of the peptide into membranes with differing lipid compositions and was found to be crucial for pore formation and toxicity of the peptide to fibroblasts. The combination of biophysical data and cell-based assays suggests likely mechanisms involved in both the antibiotic and toxic activity of chrysophsins.
Mots clés
Amino Acid Sequence, Animals, Antimicrobial Cationic Peptides, chemistry, Cell Line, Cell Membrane, metabolism, Circular Dichroism, Color, Fibroblasts, Histidine, metabolism, Humans, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Protein Structure, Secondary, Sea Bream, Spectrometry, Fluorescence, Tryptophan, chemistry
Référence
Biochemistry. 2007 Dec;46(51):15175-87
