The X-ray structure of a hemipteran ecdysone receptor ligand-binding domain - Comparison with a Lepidopteran ecdysone receptor ligand-binding domain and implications for insecticide design
The X-ray structure of a hemipteran ecdysone receptor ligand-binding domain - Comparison with a Lepidopteran ecdysone receptor ligand-binding domain and implications for insecticide design
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DOI：
10.1074/jbc.m500661200
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发表时间：
2005-06-10
影响因子：
4.8
通讯作者：
Hill, RJ
中科院分区：
文献类型：
--
作者：
Carmichael, JA;Lawrence, MC;Hill, RJ
蜕皮激素受体是节肢动物门的一种蜕皮激素依赖性转录因子，在调节发育和生殖过程中大量基因网络的表达中起着重要作用。功能性受体是两种核受体蛋白蜕皮激素受体（EcR）和超气门蛋白的异源二聚体。该受体是环境友好的双酰肼杀虫剂的靶标，其对鳞翅目有效，但对半翅目或其他几种昆虫目无效。在这里，我们提出的证据表明，双酰肼杀虫剂的大部分选择性可以在其与纯化的蜕皮激素受体配体结合结构域（LBD）异二聚体的结合水平上进行研究。我们报告的晶体结构的蜕皮激素受体LBD异源二聚体的半翅目烟粉虱（Bt，甘薯粉虱）在复杂的蜕皮激素类似物ponasterone A。虽然与鳞翅目Heliothis virescens（Hv）蜕皮激素受体的相应已知LBD结构的比较显示，在两种情况下，ponasterone A结合的总体模式非常相似，但我们观察到BtEcR蜕皮激素结合口袋的结构与HvEcR在不与ponasterone A接触的那些部分不同。我们认为，这些差异的配体结合口袋可能提供了分子基础的分类顺序选择性的双酰肼杀虫剂。
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.