Structural and functional characterization of hBD-1(Ser35), a peptide deduced from a DEFB1 polymorphism.
beta-Defensins are mammalian antimicrobial peptides that share a unique disulfide-bonding motif of six conserved cysteines. An intragenic polymorphism of the DEFB1 gene that changes a highly conserved Cys to Ser in the peptide coding region has recently been described. The deduced peptide cannot form three disulfide bonds, as one of the cysteines is unpaired. We have determined the cysteine connectivities of a corresponding synthetic hBD-1(Ser35) peptide, investigated the structure by circular dichroism spectroscopy, and assayed the in vitro antimicrobial activity. Despite a different arrangement of the disulfides, hBD-1(Ser35) proved as active as hBD-1 against the microorganisms tested. This activity likely depends on the ability of hBD-1(Ser35) to adopt an amphipathic conformation in hydrophobic environment, similar to the wild type peptide, as suggested by CD spectroscopy.
Circo
Raffaella
R
Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, P.le Kolbe, 4, 33100 Udine, Italy.
Skerlavaj
Barbara
B
Gennaro
Renato
R
Amoroso
Antonio
A
Zanetti
Margherita
M
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003455:Cryptococcus neoformans / Q000187:drug effects; D004220:Disulfides / Q000032:analysis; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012694:Serine; D023083:beta-Defensins / Q000737:chemistry* / Q000235:genetics* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; C406407:DEFB1 protein, human; D004220:Disulfides; D010446:Peptide Fragments; D010455:Peptides; D023083:beta-Defensins; D012694:Serine