title: Aggregation of cateslytin beta-sheets on negatively charged lipids promotes rigid membrane domains. A new mode of action for antimicrobial peptides?
abstract: Cateslytin, a positively charged (5+) arginine-rich antimicrobial peptide (bCgA, RSMRLSFRARGYGFR), was chemically synthesized and studied against membranes that mimic bacterial or mammalian systems. Circular dichroism, polarized attenuated total reflection infrared spectroscopy, (1)H high-resolution MAS NMR, and (2)H and (31)P solid state NMR were used to follow the interaction from peptide and membrane points of view. Cateslytin, which is unstructured in solution, is converted into antiparallel beta-sheets that aggregate mainly flat at the surface of negatively charged bacterial mimetic membranes. Arginine residues are involved in the binding to negatively charged lipids. Following the interaction of the cateslytin peptide, rigid and thicker membrane domains enriched in negatively charged lipids are found. Much less interaction is detected with neutral mammalian model membranes, as reflected by only minor percentages of beta-sheets or helices in the peptide secondary structure. No membrane destruction was detected for both bacterial and mammalian model membranes. A molecular model is proposed in which zones of different rigidity and thickness bring about phase boundary defects that ultimately lead to permeability induction and peptide crossing through bacterial membranes.
authors.affiliation: UMR 5248 CBMN, CNRS-Université Bordeaux 1-ENITAB, IECB, Pessac, France.
authors.forename: Frantz
authors.initials: F
authors.lastname: Jean-François
authors.forename: Sabine
authors.initials: S
authors.lastname: Castano
authors.forename: Bernard
authors.initials: B
authors.lastname: Desbat
authors.forename: Benoît
authors.initials: B
authors.lastname: Odaert
authors.forename: Michel
authors.initials: M
authors.lastname: Roux
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Erick J
authors.initials: EJ
authors.lastname: Dufourc
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D053379:Chromogranin A / Q000138:chemical synthesis* / Q000378:metabolism / Q000502:physiology*; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D008567:Membranes, Artificial; D008823:Micelles; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000378:metabolism / Q000502:physiology*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D053379:Chromogranin A; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D008823:Micelles; D010446:Peptide Fragments; C527456:chromogranin A (344-358)