A study of host defence peptide beta-defensin 3 in primates.
We have investigated the molecular evolution of the gene coding for beta-defensin 3 (DEFB103) in 17 primate species including humans. Unlike the DEFB4 genes (coding for beta-defensin 2) [Boniotto, Tossi, Del Pero, Sgubin, Antcheva, Santon and Masters (2003) Genes Immun. 4, 251-257], DEFB103 shows a marked degree of conservation in humans, Great Apes and New and Old World monkeys. Only the Hylobates concolor defensin hcBD3 showed an amino acid variation Arg17-->Trp17 that could have a functional implication, as it disrupts an intramolecular salt bridge with Glu27, which locally decreases the charge and may favour dimerization in the human congener hBD3. This is thought to involve the formation of an intermolecular salt bridge between Glu28 and Lys32 on another monomer [Schibli, Hunter, Aseyev, Starner, Wiencek, McCray, Tack and Vogel (2002) J. Biol. Chem. 277, 8279-8289]. To test the role of dimerization in mediating biological activity, we synthesized hBD3, hcBD3 and an artificial peptide in which the Lys26-Glu27-Glu28 stretch was replaced by the equivalent Phe-Thr-Lys stretch from human beta-defensin 1 and we characterized their structure and anti-microbial activity. Although the structuring and dimerization of these peptides were found to differ significantly, this did not appear to affect markedly the anti-microbial potency, the broad spectrum of activity or the insensitivity of the anti-microbial action to the salinity of the medium.
Boniotto
Michele
M
Department of Reproduction and Development Sciences, University of Trieste, Via dell'Istria 65/1, 34137 Trieste, Italy.
Antcheva
Nikolinka
N
Zelezetsky
Igor
I
Tossi
Alessandro
A
Palumbo
Valeria
V
Verga Falzacappa
Maria Vittoria
MV
Sgubin
Silvia
S
Braida
Laura
L
Amoroso
Antonio
A
Crovella
Sergio
S
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002520:Cercopithecidae; D014644:Genetic Variation; D006071:Gorilla gorilla; D006801:Humans; D016674:Hylobatidae; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D011148:Pongo pygmaeus; D011323:Primates; D012452:Saguinus; D023083:beta-Defensins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C422950:DEFB103A protein, human; D023083:beta-Defensins