Institute for Molecular Bioscience and School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia QLD 4072, Australia.
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10478-83. doi: 10.1073/pnas.1103501108. Epub 2011 Jun 13.
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.
三硫键抑制剂胱氨酸结（ICK）基序是蜘蛛、蝎子和水生锥形蜗牛毒液肽共有的一种折叠结构。十多年前，有人提出 ICK 基序是一种经过修饰的祖先二硫键折叠结构，称为二硫键导向β发夹（DDH）。本文报道了一种新型毒素[U(1)-liotoxin-Lw1a（U(1)-LITX-Lw1a）]的分离、鉴定和结构，该毒素来自蝎子 Liocheles waigiensis 的毒液，是第一个采用 DDH 折叠的天然肽。U(1)-LITX-Lw1a 不仅代表了毒液蛋白进化中缺失环节的发现，也是蝎子毒液肽采用的第四个结构折叠的第一个成员。此外，我们还表明 U(1)-LITX-Lw1a 对多种害虫具有很强的杀虫活性，从而为生物杀虫剂的开发提供了一个独特的结构支架。
