Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9

• Published in: The FEBS journal Vol. 275; no. 16; pp. 4134 - 4151
• Main Authors: Auvynet, Constance, El Amri, Chahrazade, Lacombe, Claire, Bruston, Francine, Bourdais, Julie, Nicolas, Pierre, Rosenstein, Yvonne
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.08.2008; Blackwell Publishing Ltd; Wiley
• Subjects: Amino Acid Sequence; Amyloid - chemistry; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptide; Anura; Biochemistry; Chemical Sciences; Chemotactic Factors - chemistry; Chemotactic Factors - pharmacology; chemotaxis; Chemotaxis - drug effects; dermaseptin; frog skin; Frogs; infrared spectroscopy; Lipid Bilayers - chemistry; Molecular Sequence Data; Molecular structure; Organic chemistry; Peptides; Protein Structure, Secondary; Receptors, G-Protein-Coupled - metabolism; Water
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2008.06554.x

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 α-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 β-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 Aβ(1-42), the most fibrillogenic isoform of amyloid beta peptides, and the prion peptide PrP(106-126).