Membrane interaction of chrysophsin-1, a histidine-rich antimicrobial peptide from red sea bream.
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.
Mason
A James
AJ
UMR 7177, Institut de Chimie, Université Louis Pasteur/CNRS, 4 rue Blaise Pascal, 67070 Strasbourg, France. james.mason@kcl.ac.uk
Bertani
Philippe
P
Moulay
Gilles
G
Marquette
Arnaud
A
Perrone
Barbara
B
Drake
Alex F
AF
Kichler
Antoine
A
Bechinger
Burkhard
B
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D003116:Color; D005347:Fibroblasts; D006639:Histidine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D021541:Sea Bream; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
D023181:Antimicrobial Cationic Peptides; C472594:chrysophsin; D006639:Histidine; D014364:Tryptophan