8.B.20 The Australian Scorpion Toxin (Liotoxin) Family

The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. It has been proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Smith et al. 2011 reported the isolation, characterization, and structure of a novel toxin [U(1)-liotoxin-Lw1a (U(1)-LITX-Lw1a)] (Liotoxin) from the venom of the scorpion Liocheles waigiensis. It is the first example of a native peptide that adopts the DDH fold. Liotoxin 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, Smith et al. 2011 showed that Liotoxin has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development.  It appears to impair the activities of ryanodine-sensitive Ca²⁺ release channels.