Carmichael Jennifer A, Lawrence Michael C, Graham Lloyd D, Pilling Patricia A, Epa V Chandana, Noyce Leonie, Lovrecz George, Winkler David A, Pawlak-Skrzecz Anna, Eaton Ruth E, Hannan Garry N, Hill Ronald J
CSIRO Health Sciences and Nutrition, 343 Royal Parade, Parkville, Victoria 3052, Australia.
J Biol Chem. 2005 Jun 10;280(23):22258-69. doi: 10.1074/jbc.M500661200. Epub 2005 Apr 4.
The ecdysone receptor is a hormone-dependent transcription factor that plays a central role in regulating the expression of vast networks of genes during development and reproduction in the phylum Arthropoda. The functional receptor is a heterodimer of the two nuclear receptor proteins ecdysone receptor (EcR) and ultraspiracle protein. The receptor is the target of the environmentally friendly bisacylhydrazine insecticides, which are effective against Lepidoptera but not against Hemiptera or several other insect orders. Here we present evidence indicating that much of the selectivity of the bisacylhydrazine insecticides can be studied at the level of their binding to purified ecdysone receptor ligand-binding domain (LBD) heterodimers. We report the crystal structure of the ecdysone receptor LBD heterodimer of the hemipteran Bemisia tabaci (Bt, sweet potato whitefly) in complex with the ecdysone analogue ponasterone A. Although comparison with the corresponding known LBD structure from the lepidopteran Heliothis virescens (Hv) ecdysone receptor revealed the overall mode of ponasterone A binding to be very similar in the two cases, we observed that the BtEcR ecdysteroid-binding pocket is structured differently to that of HvEcR in those parts that are not in contact with ponasterone A. We suggest that these differences in the ligand-binding pocket may provide a molecular basis for the taxonomic order selectivity of bisacylhydrazine insecticides.
蜕皮激素受体是一种激素依赖性转录因子，在节肢动物门的发育和繁殖过程中，对大量基因网络的表达调控起着核心作用。功能性受体是两种核受体蛋白——蜕皮激素受体（EcR）和超气门蛋白的异二聚体。该受体是环境友好型双酰肼类杀虫剂的作用靶点，这类杀虫剂对鳞翅目昆虫有效，但对半翅目或其他几个昆虫目无效。在此，我们提供证据表明，双酰肼类杀虫剂的许多选择性可以在其与纯化的蜕皮激素受体配体结合域（LBD）异二聚体结合的水平上进行研究。我们报道了半翅目烟粉虱（Bt，甘薯粉虱）蜕皮激素受体LBD异二聚体与蜕皮激素类似物紫衫甾酮A复合物的晶体结构。尽管与鳞翅目棉铃虫（Hv）蜕皮激素受体相应的已知LBD结构比较显示，紫衫甾酮A的总体结合模式在两种情况下非常相似，但我们观察到，在不与紫衫甾酮A接触的部分，BtEcR蜕皮甾体结合口袋的结构与HvEcR不同。我们认为，配体结合口袋的这些差异可能为双酰肼类杀虫剂的分类目选择性提供分子基础。
