title: Effects of positively selected sequence variations in human and Macaca fascicularis beta-defensins 2 on antimicrobial activity.
abstract: The evolution of orthologous genes coding for beta-defensin 2 (BD2) in primates has been subject to positive selection during the divergence of the platyrrhines from the catarrhines and of the Cercopithecidae from the Hylobatidae, great apes, and humans. Three peptides have been selected for a functional analysis of the effects of sequence variations on the direct antimicrobial activity: human BD2 (hBD2), Macaca fascicularis BD2 (mfaBD2), and a variant of the human peptide lacking Asp(4), (-D)hBD2, which is characteristic only of the human/great ape peptides. hBD2 and mfaBD2 showed a significant difference in specificity, the former being more active towards Escherichia coli and the later towards Staphylococcus aureus and Candida albicans. Asp(4) in the human peptide appears to be important, as (-D)hBD2 was less structured and had a markedly lower antimicrobial activity. The evolution of beta-defensin 2 in primates may thus have been driven, at least in part, by different environmental pressures so as to modulate antimicrobial activity.
authors.affiliation: Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, I-34127 Trieste, Italy.
authors.forename: Nikolinka
authors.initials: N
authors.lastname: Antcheva
authors.forename: Michele
authors.initials: M
authors.lastname: Boniotto
authors.forename: Igor
authors.initials: I
authors.lastname: Zelezetsky
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pacor
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Verga Falzacappa
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tossi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003593:Cytoplasm / Q000187:drug effects; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D007700:Kinetics; D008252:Macaca fascicularis; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013045:Species Specificity; D013329:Structure-Activity Relationship; D023083:beta-Defensins / Q000235:genetics* / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; C106641:DEFB4A protein, human; D023083:beta-Defensins; D001616:beta-Galactosidase