Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif

Publication Type:
Journal Article
Citation:
Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 (26), pp. 10478 - 10483
Issue Date:
2011-06-28
Full metadata record
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.
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