title: Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9.
abstract: Dermaseptin S9 (Drs S9), GLRSKIWLWVLLMIWQESNKFKKM, isolated from frog skin, does not resemble any of the cationic and amphipathic antimicrobial peptides identified to date, having a highly hydrophobic core sequence flanked at either side by cationic termini. Previous studies [Lequin O, Ladram A, Chabbert A, Bruston F, Convert O, Vanhoye D, Chassaing G, Nicolas P & Amiche M (2006) Biochemistry45, 468-480] demonstrated that this peptide adopted a non-amphipathic alpha-helical conformation in trifluoroethanol/water mixtures, but was highly aggregated in aqueous solutions and in the presence of sodium dodecyl sulfate micelles. Circular dichroism, FTIR and attenuated total reflectance FTIR spectroscopies, combined with a surface plasmon resonance study, show that Drs S9 forms stable and ordered beta-sheet aggregates in aqueous buffers or when bound to anionic or zwitterionic phospholipid vesicles. These structures slowly assembled into amyloid-like fibrils in aqueous environments via spherical intermediates, as revealed by electron microscopy and Congo red staining. Drs S9 induced the directional migration of neutrophils, T lymphocytes and monocytes. Interestingly, the antimicrobial and chemotactic activities of Drs S9 are modulated by its amyloid-like properties. Whereas spherical oligomers of Drs S9 exhibit antimicrobial activity, the soluble, weakly self-associated forms of Drs S9 act on human leukocytes to promote chemotaxis and/or immunological response activation in the same range of concentration as amyloidogenic peptides Abeta(1-42), the most fibrillogenic isoform of amyloid beta peptides, and the prion peptide PrP(106-126).
authors.affiliation: UPMC Université de Paris 06, CNRS FRE 2852, Peptidome de la Peau des Amphibiens, Paris Cedex 5, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Auvynet
authors.forename: Chahrazade
authors.initials: C
authors.lastname: El Amri
authors.forename: Claire
authors.initials: C
authors.lastname: Lacombe
authors.forename: Francine
authors.initials: F
authors.lastname: Bruston
authors.forename: Julie
authors.initials: J
authors.lastname: Bourdais
authors.forename: Pierre
authors.initials: P
authors.lastname: Nicolas
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rosenstein
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002630:Chemotactic Factors / Q000737:chemistry* / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000682:Amyloid; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002630:Chemotactic Factors; D008051:Lipid Bilayers; D043562:Receptors, G-Protein-Coupled; C508965:dermaseptin S9, Phyllomedusa sauvagei