Structural features of distinctin affecting peptide biological and biochemical properties(801 views) Dalla Serra M, Cirioni O, Vitale RM, Renzone G, Coraiola M, Giacometti A, Potrich C, Baroni E, Guella G, Sanseverino M, De Luca S, Scalise G, Amodeo P, Scaloni A
Bruno Kessler Foundation, Institute of Biophysics, National Research Council, 38100 Povo (Trento), Italy
Institute of Infectious Diseases and Public Health, Polytechnic Marche University, 60200 Ancona, Italy
Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli (Naples), Italy
Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy
Laboratory of Bioorganic Chemistry, Department of Physics, University of Trento, 38100 Povo (Trento), Italy
Inbios S.r.l., 80078 Pozzuoli (Naples), Italy
Institute of Biostructures and Bioimages, National Research Council, 80138 Naples, Italy
Inbios S. r. l., 80078 Pozzuoli (Naples), Italy
References: Not available.
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.
Structural features of distinctin affecting peptide biological and biochemical properties