Oral Presentation The 16th Australian Peptide Conference 2025

Discovery of Stinging Nettle Neurotoxins (128338)

Thomas Durek 1 , Marie Tuifua 1 , Sam Robinson 1 , David Craik 1 , Irina Vetter 1
  1. University of Queensland, Brisbane, QLD, Australia

Stinging nettles produce painful effects on humans that can last for days. The activity has previously been attributed to small molecules, but these compounds cannot explain the observed sensory effects. We show here that the ‘venoms’ of these plants contain heretofore unknown pain-inducing peptides. These neurotoxins disrupt membranes or can potently activate neurons and delay inactivation of sodium channels. The peptides are structurally diverse and can be grouped into 3 classes: inhibitory cystine knot peptides (ICK), thionins and double knot toxins. 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.

  1. Gilding, E. K.; Jami, S.; Deuis, J. R.; Israel, M. R.; Harvey, P. J.; Poth, A. G.; Rehm, F. B. H.; Stow, J. L.; Robinson, S. D.; Yap, K.; Brown, D. L.; Hamilton, B. R.; Andersson, D.; Craik, D. J.; Vetter, I.; Durek, T., Neurotoxic peptides from the venom of the giant Australian stinging tree. Sci. Adv. 2020, 6, eabb8828.
  2. Xie, J.; Robinson, S. D.; Gilding, E. K.; Jami, S.; Deuis, J. R.; Rehm, F. B. H.; Yap, K.; Ragnarsson, L.; Chan, L. Y.; Hamilton, B. R.; Harvey, P. J.; Craik, D. J.; Vetter, I.; Durek, T., Neurotoxic and cytotoxic peptides underlie the painful stings of the tree nettle Urtica ferox. J. Biol. Chem. 2022, 298, 102218.