Poster Presentation 2014 International Biophysics Congress

Weaponization of a hormone: Convergent recruitment of hyperglycemic hormone into arthropod venoms (#637)

Eivind A.B. Undheim 1 2 , Mehdi Mobli 2 , Lena L. Grimm 1 , Chek-Fong Low 1 , David Morgenstern 1 , Volker Herzig 1 , Pamela Zobel-Thropp 3 , Sandy P. Gonzalez 1 , Bryan G. Fry 4 , Greta Binford 3 , Glenn F. King 1
  1. Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD, Australia
  2. Centre for Advanced Imaging, University of Queensland, St Lucia, QLD, Australia
  3. Department of Biology, Lewis & Clark College, Portland, Oregon, USA
  4. School of Biological Sciences, University of Queensland, St. Lucia, QLD, Australia

Arthropod venoms are complex cocktails containing up to thousands of unique compounds. Most venoms consist primarily of proteins and small (<10 kDa) disulfide-rich peptides recruited into the venom from “housekeeping” roles. These peptides are commonly recruited from endogenous body proteins and subsequently mutated to yield neofunctionalised toxins that display high specificity and affinity for specific subtypes of ion channels and membrane receptors. Remarkably, however, the evolutionary history of these toxins remains poorly understood. Here, we show how a neuropeptide hormone has been convergently recruited into the venom of spiders and centipedes through divergent modification of the ancestral gene. High-resolution structural analysis of representative toxins from these animals show that these toxins have a unique structure and disulfide framework, and that a key step in converting the ancestral hormone into a toxin has involved the loss of a C-terminal α-helix. We show that centipedes have additionally modified a splice site in the ancestral gene to yield a unique structural change resulting in a highly stable fold that is resistant to extreme denaturing conditions. Our results raise a new paradigm for toxin evolution in spiders and centipedes, and highlight the value of structural information in providing insight into toxin evolution.