pWe have investigated the molecular evolution of the gene coding for β-defensin 3 (DEFB103) in 17 primate species including humans. Unlike the DEFB4 genes (coding for β-defensin 2) [Boniotto, Tossi, Del Pero, Sgubin, Antcheva, Santon and Masters (2003) Genes Immun. b4/b, 251–257], DEFB103 shows a marked degree of conservation in humans, Great Apes and New and Old World monkeys. Only the iHylobates concolor/i defensin hcBD3 showed an amino acid variation Argsup17/sup→Trpsup17/sup that could have a functional implication, as it disrupts an intramolecular salt bridge with Glusup27/sup, 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 Glusup28/sup and Lyssup32/sup on another monomer [Schibli, Hunter, Aseyev, Starner, Wiencek, McCray, Tack and Vogel (2002) J. Biol. Chem. b277/b, 8279–8289]. To test the role of dimerization in mediating biological activity, we synthesized hBD3, hcBD3 and an artificial peptide in which the Lyssup26/sup-Glusup27/sup-Glusup28/sup stretch was replaced by the equivalent Phe-Thr-Lys stretch from human β-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./p
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