在ecdysone激素受体的联结口袋中的结构适应性
Isabelle M L Billas1, Thomas Iwema, Jean-Marie Garnier
1Département de Biologie et de Génomique Structurales, IGBMC, CNRS/INSERM/Université Louis Pasteur, Parc d'Innovation BP10142, 67404 Illkirch cedex, France.
昆虫的ecdysone受体 (EcR) 和ultraspiracle (USP) 异构体晶体结构显示出不同的联结口袋. 这一发现为设计有针对性的,对环境安全的杀虫剂提供了新的途径.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 昆虫内分泌学 昆虫内分泌学
背景情况:
- 雌激素激素通过核转录因子的雌激素受体 (EcR) 调节昆虫的发育.
- 对于配体和DNA结合,EcR需要与超螺旋体 (USP) 进行异体化,这是一种视网膜-X受体同类物.
研究的目的:
- 确定结晶结构的Heliothis virescens EcR-USP异构体结合一个类固醇的ecdysteroid和一个非类固醇的agonist.
- 为了研究昆虫核受体中连接体结合和异构聚变的结构基础.
- 为设计新型,特定于昆虫的杀虫剂提供见解.
主要方法:
- 使用X射线晶体学来确定EcrR-USP联体结合域的结构.
- 复合物与波纳斯特A (类固醇) 和BII06830 (非类固醇激动剂) 形成.
- 对联结状态的比较结构分析.
主要成果:
- 解决了EcR-USP异构体的晶体结构,其中包括类固醇和非类固醇配体.
- 进行比较时发现,类固醇和非类固醇联体的联体结合口袋显著不同且部分重叠.
- 在脊椎动物和无脊椎动物中强调了EcR-USP异构化的普遍性.
结论:
- 昆虫核受体异构化是一种保存机制.
- 在EcR中的联结口袋具有适应性,可以容纳多种联结体.
- 结构性见解为开发有针对性的,环境安全的杀虫剂铺平了道路,并对人类核受体研究产生影响.
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