Structural features of distinctin affecting peptide biological and biochemical properties.
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.
Dalla Serra
Mauro
M
Bruno Kessler Foundation, Institute of Biophysics, National Research Council, 38100 Povo, Trento, Italy.
Cirioni
Oscar
O
Vitale
Rosa Maria
RM
Renzone
Giovanni
G
Coraiola
Manuela
M
Giacometti
Andrea
A
Potrich
Cristina
C
Baroni
Elisa
E
Guella
Graziano
G
Sanseverino
Marina
M
De Luca
Stefania
S
Scalise
Giorgio
G
Amodeo
Pietro
P
Scaloni
Andrea
A
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
D000900:Anti-Bacterial Agents; D008081:Liposomes; D010455:Peptides