posters 5th Asia-Pacific NMR Symposium 2013

Weaponization of a hormone: Convergent recruitment of hyperglycemic hormone into arthropod venoms.  (#215)

Eivind A.B. Undheim 1 , Mehdi Mobli 1 , Lena L. Grimm 1 , Chek-Fong Low 1 , David Morgenstern 1 , Volker Herzig 1 , Pamela Zobel-Thropp 2 , Sandy P Gonzalez 1 , Shilong Yang 3 , Ren Lai 3 , Bryan G Fry 4 , Greta Binford 2 , Glenn F King 1
  1. Institute for Molecular Bioscience, UQ, St Lucia, QLD, Australia
  2. Department of Biology, Lewis & Clark College, Portland, Oregon, USA
  3. Kunming Institute of Zoology, Chinese Academy of Sciences & Yunnan Province, Kunming, Yunnan, China
  4. School of Biological Sciences, The University of Queensland, St Lucia, Queensland, Australia

Arthropod venoms are complex cocktails containing up to thousands of unique compounds. In most cases, these compounds consist primarily of proteins and disulfide-rich peptides recruited into the venom from “housekeeping” roles1. While proteins are often readily assigned an ancestral type, the origins of disulfide-rich venom peptides (toxins) are usually shrouded by extreme sequence variation caused by regimes of positive selection that tend to drive their evolution. In contrast, the overall tertiary structures, or structural scaffolds, of toxins are often highly conserved and thereby retain valuable information on ancestry and phylogenetic relationships. Here we present the application of toxin 3D structures in unravelling the molecular and structural evolution of a set of convergently recruited small (<6 kDa) disulfide-rich toxins. 13C/15N-labelled toxins were produced by recombinant expression in E. coli, and the structure solved by multidimensional NMR.

Structural studies of the insecticidal toxin TaITX-1 from the American Hobo spider (Tegenaria agrestis) first revealed its three-dimensional structure to be homologous with that of moult-inhibiting hormone (MIH). MIH is a member of the crustacean hyperglycaemic hormone (CHH) family, which is ubiquitous in arthropods and includes a large number of small (<10 kDa), highly helical, disulfide rich peptides with a broad range of functions. Sequence search by BLAST showed this family has also been recruited into venoms of parasitoid wasps (Microctonus spp.) and centipedes (Scolopendra spp.). Moreover, structure determination of two recently reported toxins from the Chinese Red-headed centipede (S. subspinipes), µ-SLPTX-Ssm6a2 and κ-SLPTX-Ssm1a3, revealed these to be derived forms of centipede venom CHH. Both µ-SLPTX-Ssm6a and κ-SLPTX-Ssm1a exhibit remarkable stability, and structure-guided sequence alignments suggest a number of adaptations that have enabled this feature. 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.

  1. Fry, B. G., et al. (2009) The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms. Annu. Rev. Genomics Hum. Genet. 10, 483-511.
  2. Yang S., et al. (2012) Chemical punch packed in venoms makes centipedes excellent predators. Mol Cell Proteomics 11, 640-50.
  3. Yang S., et al. (2013) Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc. Natl. Acad. Sci. USA In press (Accepted 05/09-13).