Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor

被引:199
作者
Billas, IML [1 ]
Iwema, T [1 ]
Garnier, JM [1 ]
Mitschler, A [1 ]
Rochel, N [1 ]
Moras, D [1 ]
机构
[1] Univ Strasbourg 1, IGBMC, Dept Biol & Genom Struct, CNRS,INSERM, F-67404 Illkirch Graffenstaden, France
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature02112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The ecdysteroid hormones coordinate the major stages of insect development, notably moulting and metamorphosis, by binding to the ecdysone receptor (EcR); a ligand-inducible nuclear transcription factor(1,2). To bind either ligand or DNA, EcR must form a heterodimer with ultraspiracle (USP), the homologue of retinoid-X receptor(3-5). Here we report the crystal structures of the ligand-binding domains of the moth Heliothis virescens EcR - USP heterodimer in complex with the ecdysteroid ponasterone A and with a non-steroidal, lepidopteran-specific agonist BYI06830 used in agrochemical pest control. The two structures of EcR - USP emphasize the universality of heterodimerization as a general mechanism common to both vertebrates and invertebrates. Comparison of the EcR structures in complex with steroidal and non-steroidal ligands reveals radically different and only partially overlapping ligand-binding pockets that could not be predicted by molecular modelling and docking studies(6,7). These findings offer new perspectives for the design of insect-specific, environmentally safe insecticides. The concept of a ligand-dependent binding pocket in EcR provides an insight into the moulding of nuclear receptors to their ligand, and has potential applications for human nuclear receptors.
引用
收藏
页码:91 / 96
页数:6
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