Solution structure of a defensin-like peptide from platypus venom

Abstract

Three defensin-like peptides (DLPs) were isolated from platypus venom and sequenced. One of these peptides, DLP-1, was synthesized chemically and its three-dimensional structure was determined using NMR spectroscopy. The main structural elements of this 42-residue peptide were an anti-parallel beta-sheet comprising residues 15-18 and 37-40 and a small 3(10) helix spanning residues 10-12. The overall three-dimensional fold is similar to that of beta-defensin-12, and similar to the sodium-channel neurotoxin ShI (Stichodactyla helianthus neurotoxin I). However, the side chains known to be functionally important in beta-defensin-12 and ShI are not conserved in DLP-1, suggesting that it has a different biological function. Consistent with this contention, we showed that DLP-1 possesses no anti-microbial properties and has no observable activity on rat dorsal-root-ganglion sodium-channel currents.

Venom evolution through gene duplications

“…In platypus, we have found that three venom defensin-like peptides, a major component of platypus venom, have evolved through tandem duplications from antimicrobial beta-defensin genes (Torres et al, 1999;Torres et al, 2000;Whittington et al, 2008aWhittington et al, , 2008b. The absence of antimicrobial activity in these venom peptides suggests that the duplicated copies have taken on specialized roles in venom (Whittington et al, 2008b).…”

“…It is likely that platypus venom does not require the added dosage effects and functional diversification gained through gene duplications that are important in more potent venoms. Indeed, the potency of platypus venom has been found to be considerably weaker than snake (Torres et al, 1999). The function of platypus venom appears to be used for asserting dominance over competitors during the breeding season as only the males of the species are venomous and venom is only actively produced during the breeding season (Whittington and Belov, 2007).…”

Human β-defensins

“…A possible evolutionary relation is strongly supported by current structural information [177,186,187]. The defensin-like fold has been observed for various toxins, including snake toxins [183,187], sea anemone toxins [188,189] and platypus venom toxins (defensin-like peptides, DLP1 and DLP-2) [178,190,191]. Curiously, platypus DLPs have neither antimicrobial nor mytotoxic properties, and their roles as the components of the venom are unknown [178].…”

“…Multiple sequence alignment [170] and ribbon representations of four different molecules from β-defensin-fold family. The PDB accession codes are 1FD3 (hBD-2, [165]), 1BNB (bBD-12, [184]), (Sphe-2, [183]) and 1B8W (DLP-2, [190]). The six conserved Cys residues and moderately conserved Gly residue are shown in yellow and blue, respectively.…”

Recent aspects of chemical ecology: Natural toxins, coral communities, and symbiotic relationships

“…Since this poison was shown to be toxic against rabbits at the end of the 19 th century, the extracts of secreted venom or poison gland have been well investigated [34][35][36]. Several biologically active peptides and proteins have been identified from this venom, i.e., defensin-like peptides [37,38], C-type natriuretic peptides (ovCNPs) [39][40][41], nerve growth factor, and hyaluronidase. OvCNP-39 causes the relaxation of rat uterine smooth muscle, promotes histamine release from mast cells, and forms fast cation channels in lipid bilayers [42][43][44].…”