具有假定祖先结构的独特蝎毒素为抑制性半胱氨酸结基序的进化提供了线索。
Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif.
机构信息
Institute for Molecular Bioscience and School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia QLD 4072, Australia.
出版信息
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10478-83. doi: 10.1073/pnas.1103501108. Epub 2011 Jun 13.
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.
摘要
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。
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