A study of host defence peptide β-defensin 3 in primates

Boniotto, Michele; Antcheva, Nikolinka; Zelezetsky, Igor; Tossi, Alessandro; Palumbo, Valeria; Falzacappa, Maria Vittoria Verga; Sgubin, Silvia; Braida, Laura; Amoroso, Antonio; Crovella, Sérgio

doi:10.1042/bj20030528

Cited by 71 publications

(92 citation statements)

References 21 publications

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“…Staphylococcus aureus with Defb14 reveal that its antibacterial activity (minimum bactericidal concentrations of 1.5 and 3 g/ml, respectively) ( Table 2) is comparable with that reported for HBD3 (1,10,32). Unlike Defr1 (21), antimicrobial activity against both organisms is not altered upon reduction with dithiothreitol, indicating that its antimicrobial action is independent of the disulfide oxidation state.…”

Section: Hbd3 ␤-Defensin Derivatives As Antimicrobial Peptides Linearsupporting

confidence: 57%

Analysis and Separation of Residues Important for the Chemoattractant and Antimicrobial Activities of β-Defensin 3

Taylor

Clarke

McCullough

et al. 2008

Journal of Biological Chemistry

102

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␤-Defensins are important in mammalian immunity displaying both antimicrobial and chemoattractant activities. Three canonical disulfide intramolecular bonds are believed to be dispensable for antimicrobial activity but essential for chemoattractant ability. However, here we show that HBD3 (human ␤-defensin 3) alkylated with iodoactemide and devoid of any disulfide bonds is still a potent chemoattractant. Furthermore, when the canonical six cysteine residues are replaced with alanine, the peptide is no longer active as a chemoattractant. These findings are replicated by the murine ortholog Defb14. We restore the chemoattractant activity of Defb14 and HBD3 by introduction of a single cysteine in the fifth position (Cys V ) of the ␤-defensin six cysteine motif. In contrast, a peptide with a single cysteine at the first position (Cys I ) is inactive. Moreover, a range of overlapping linear fragments of Defb14 do not act as chemoattractants, suggesting that the chemotactic activity of this peptide is not dependent solely on an epitope surrounding Cys V . Full-length peptides either with alkylated cysteine residues or with cysteine residues replaced with alanine are still strongly antimicrobial. Defb14 peptide fragments were also tested for antimicrobial activity, and peptides derived from the N-terminal region display potent antimicrobial activity. Thus, the chemoattractant and antimicrobial activities of ␤-defensins can be separated, and both of these functions are independent of intramolecular disulfide bonds. These findings are important for further understanding of the mechanism of action of defensins and for therapeutic design.

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Section: Hbd3 ␤-Defensin Derivatives As Antimicrobial Peptides Linearsupporting

confidence: 57%

Analysis and Separation of Residues Important for the Chemoattractant and Antimicrobial Activities of β-Defensin 3

Taylor

Clarke

McCullough

et al. 2008

Journal of Biological Chemistry

102

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“…refs. [60,61]). However, from the pairwise comparisons, it is difficult to infer which sites are positively or negatively selected.…”

Section: Discussionmentioning

confidence: 99%

Adaptive evolution after duplication of penaeidin antimicrobial peptides

Padhi

Verghese

Otta

et al. 2007

Fish & Shellfish Immunology

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Penaeidin antimicrobial peptides in penaeid shrimps are an important component of their innate immune system that provides immunity against infection caused by several gram-positive bacteria and filamentous fungal species. Despite the knowledge on the identification and characterization of these peptides in penaeid shrimps, little is known about the evolutionary pattern of these peptides and the underlying genetic mechanisms that maintain high sequence diversities in the penaeidin gene family. Based on the phylogenetic analyses and maximum likelihood-based codon substitution analyses, here we present the convincing evidence that multiple copies of penaeidins have evolved by gene duplication, and positive Darwinian selection (adaptive evolution) is the likely cause of accelerated rate of amino acid substitutions among these duplicated genes.While the average ratio of non-synonymous to synonymous substitutions (u) for the entire coding region of both active domains is 0.9805, few codon sites showed significantly higher u (3.73). The likelihood ratio tests that compare models incorporating positive selection (u > 1) at certain codon sites with models not incorporating positive selection (u < 1), failed to reject (p ¼ 0) the evidence of positive Darwinian selection. The rapid adaptive evolution of this gene family might be directed by the pathogens and the faster rate of amino acid substitutions in the N-terminal proline-rich and C-terminal cysteine-rich domains could be due to their direct involvement in the protection against pathogens. When the host expose to different habitats/environment an accelerated rate of amino acid substitutions in both the active domains may also be expected.

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“…3 Based on their size and the spatial position of the six cysteine residues, animal defensins are classified as a-, b-, y-defensins of vertebrates (mammalia and birds) and insect defensins. To date, vertebrate defensins were identified in numerous species: mice, [6][7][8] birds-where they are called gallinacins- 9 rats, 10 cattle, 11,12 goats, 13 sheeps, 14 humans, 8,15,16 and non-human primates [17][18][19][20] (reviewed in Martin et al, 4 Hughes, 21 Schroder, 22 and Lehrer and Ganz 23 ). Interestingly, domestic cattle (Bos taurus) was shown to share a broad spectrum of different b-defensins, for example, tap (tracheal antimicrobial peptide), lap (lingual antimicrobial peptide), bnbd (bovine neutrophil peptide), nbd12 (neutrophil beta defensin 12), and ebd (enteric beta defensin).…”

Section: Introductionmentioning

confidence: 99%

Variability and evolution of bovine β-defensin genes

Luenser

Ludwig

2004

Genes Immun

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Defensins comprise an important family of antimicrobial peptides. Among vertebrates numerous defensin genes have been detected, but their evolutionary background is still discussed. We investigated the molecular evolution of bovine defensins via screening of different bovine species including the extinct ancestor of domestic cattle (Bos primigenius) for b-defensin encoding genes. We detected a large variability of new defensin encoding sequences similar to previously published bovine neutrophil b-defensin (bnbd), neutrophil b-defensin 12 (nbd12), enteric b-defensin (ebd), lingual antimicrobial peptide (lap), and tracheal antimicrobial peptide (tap). Our data suggest that variants of the same so-called subfamily (tap, lap, ebd, and nbd12) each share a common ancestry independent of their species origin, implicating several duplication events of tap, lap, ebd, and nbd12 before the different bovine lineages diverged. Variants of bovine neutrophil b-defensins bnbd5 and bnbd9 were detected exclusively in domestic cattle and aurochs. Values of synonymous and nonsynonymous substitutions demonstrated lap, bnbd5, bnbd9 and nbd12 evolving under positive selection, whereas amino-acid altering substitutions among variants of ebd and tap are purified. Comparison of the amino-acid sequences with available structures of human and murine defensins suggested conservation of the typical secondary elements of defensins in the absence of high sequence similarity.

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A study of host defence peptide β-defensin 3 in primates

Cited by 71 publications

References 21 publications

Analysis and Separation of Residues Important for the Chemoattractant and Antimicrobial Activities of β-Defensin 3

Analysis and Separation of Residues Important for the Chemoattractant and Antimicrobial Activities of β-Defensin 3

Adaptive evolution after duplication of penaeidin antimicrobial peptides

Variability and evolution of bovine β-defensin genes

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