title: Structural features of distinctin affecting peptide biological and biochemical properties.
abstract: The antimicrobial peptide distinctin consists of two peptide chains linked by a disulfide bridge; it presents a peculiar fold in water resulting from noncovalent dimerization of two heterodimeric molecules. To investigate the contribution of each peptide chain and the S-S bond to distinctin biochemical properties, different monomeric and homodimeric peptide analogues were synthesized and comparatively evaluated with respect to the native molecule. Our experiments demonstrate that the simultaneous occurrence of both peptide chains and the disulfide bond is essential for the formation of the quaternary structure of distinctin in aqueous media, able to resist protease action. In contrast, distinctin and monomeric and homodimeric analogues exhibited comparable antimicrobial activities, suggesting only a partial contribution of the S-S bond to peptide killing effectiveness. Relative bactericidal properties paralleled liposome permeabilization results, definitively demonstrating that microbial membranes are the main target of distinctin activity. Various biophysical experiments performed in membrane-mimicking media, before and after peptide addition, provided information about peptide secondary structure, lipid bilayer organization, and lipid-peptide orientation with respect to membrane surface. These data were instrumental in the generation of putative models of peptide-lipid supramolecular pore complexes.
authors.affiliation: Bruno Kessler Foundation, Institute of Biophysics, National Research Council, 38100 Povo, Trento, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Dalla Serra
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Vitale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Renzone
authors.forename: Manuela
authors.initials: M
authors.lastname: Coraiola
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Cristina
authors.initials: C
authors.lastname: Potrich
authors.forename: Elisa
authors.initials: E
authors.lastname: Baroni
authors.forename: Graziano
authors.initials: G
authors.lastname: Guella
authors.forename: Marina
authors.initials: M
authors.lastname: Sanseverino
authors.forename: Stefania
authors.initials: S
authors.lastname: De Luca
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
authors.forename: Pietro
authors.initials: P
authors.lastname: Amodeo
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002850:Chromatography, Gel; D003198:Computer Simulation; D019281:Dimerization; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D010455:Peptides