title: Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif.
abstract: The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U(1)-liotoxin-Lw1a (U(1)-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U(1)-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U(1)-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development.
authors.affiliation: Institute for Molecular Bioscience and School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia QLD 4072, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Smith
authors.forename: Justine M
authors.initials: JM
authors.lastname: Hill
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Little
authors.forename: Graham M
authors.initials: GM
authors.lastname: Nicholson
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D003553:Cystine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009498:Neurotoxins; D012604:Scorpion Venoms; D003553:Cystine