Effects of positively selected sequence variations in human and Macaca fascicularis beta-defensins 2 on antimicrobial activity.
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.
Antcheva
Nikolinka
N
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, I-34127 Trieste, Italy.
Boniotto
Michele
M
Zelezetsky
Igor
I
Pacor
Sabrina
S
Verga Falzacappa
Maria Vittoria
MV
Crovella
Sergio
S
Tossi
Alessandro
A
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
D000890:Anti-Infective Agents; C106641:DEFB4A protein, human; D023083:beta-Defensins; D001616:beta-Galactosidase