Defensin-like peptide-2 from platypus venom: member of a class of peptideswith a distinct structural fold

The venom of the male Australian duck-billed platypus contains a family of four polypeptides of appox. 5 kDa, which are referred to as defensin-like p eptides (DLPs). They are unique in that their amino acid sequences have no significant similarities to those of any known peptides; however, the terti ary structure of one of them, DLP-1, has recently been shown to be similar to beta-defensin-12 and to the sodium neurotoxin peptide ShI (Stichodactyla helianthus neurotoxin I). Although DLPs are the major peptides in the plat ypus venom, little is known about their biological roles. In this study, we determined the three-dimensional structure of DLP-2 by NMR spectroscopy, w ith the aim of gaining insights into the natural function of the DLPs in pl atypus venom. The DLP-2 structure was found to incorporate a short helix th at spans residues 9-12, and an antiparallel beta-sheet defined by residues 15-18 and 37-40. The overall fold and cysteine-pairing pattern of DLP-2 wer e found to be similar to those of DLP-1, and hence beta-defensin-12; howeve r, the sequence similarities between the three molecules are relatively sma ll. The distinct structural fold of the DLP-1, DLP-2, and beta-defensin-12 is based upon several key residues that include six cysteines. DLP-3 and DL P-4 are also likely to be folded similarly since they have high sequence si milarity with DLP-2. The DLPs, and beta-defensin-12 may thus be grouped tog ether into a class of polypeptide molecules which have a common or very sim ilar global fold. The fact that the DLPs did not display antimicrobial, myo toxic, or cell-growth-promoting activities implies that the nature of the s ide chains in this group of peptides is likely to play an important role in defining the biological function(s).