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- Title
Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor.
- Authors
Billas, Isabelle M. L.; Iwema, Thomas; Granier, Jean-Marie; Mitschler, André; Rochel, Natacha; Moras, Dino
- Abstract
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. To bind either ligand or DNA, EcR must form a heterodimer with ultraspiracle (USP), the homologue of retinoid-X receptor. 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. 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.
- Subjects
LIGANDS (Biochemistry); ECDYSONE; HORMONE receptors
- Publication
Nature, 2003, Vol 426, Issue 6962, p91
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature02112