Peptide Neurotoxins from Stinging Nettle ‘Venom’ — ASN Events

Peptide Neurotoxins from Stinging Nettle ‘Venom’ (#235)

Thomas Durek 1 , Jing Xie 1 , Samuel D Robinson 1 , Edward K Gilding 1 , Sina Jami 1 , Jennifer R Deuis 1 , Fabian BH Rehm 1 , Kuok Yap 1 , Lai Y Chan 1 , Peta J Harvey 1 , David J Craik 1 , Irina Vetter 1
  1. University of Queensland, Brisbane, QLD, Australia

Stinging nettles produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. The induced acute pain typically lasts for several hours, but in some cases intermittent painful flares can persist for days and weeks. The pharmacological activity has been attributed to small-molecule neurotransmitters and inflammatory mediators, but these compounds alone cannot explain the observed sensory effects. We show here that the venoms of Australian Dendrocnide species (D. moroides and D. excelsa)1 and the New Zealand tree nettle (Urtica ferox)2 contain heretofore unknown pain-inducing peptides that potently activate mouse sensory neurons and delay inactivation of voltage-gated sodium channels. These neurotoxins localize specifically to the stinging hairs and are disulfide-rich miniproteins of 4–7 kDa. The toxins can be structurally grouped into 3 classes: inhibitory cystine knot peptides (ICK, gympietides), thionins (urthionins) and a novel class of putative double ICK toxins (urticatoxins). Our results provide an intriguing example of inter-kingdom convergent evolution of animal and plant venoms with shared modes of delivery, molecular structure and pharmacology.

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