1R20

Crystal structure of the ligand-binding domains of the heterodimer EcR/USP bound to the synthetic agonist BYI06830

Summary for 1R20

• Entry DOI: 10.2210/pdb1r20/pdb
• Related: 1R1K
• Descriptor: ULTRASPIRACLE PROTEIN, ECDYSONE RECEPTOR, L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE, ... (5 entities in total)
• Functional Keywords: nuclear receptor, heterodimer, alpha-helical sandwich, structural proteomics in europe, spine, structural genomics, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Heliothis virescens (tobacco budworm); More
• Cellular location: Nucleus: O18473
• Total number of polymer chains: 2
• Total formula weight: 61264.79

Authors

Billas, I.M.L.,Iwema, T.,Garnier, J.M.,Mitschler, A.,Rochel, N.,Moras, D.,Structural Proteomics in Europe (SPINE) (deposition date: 2003-09-25, release date: 2003-11-18, Last modification date: 2024-02-14)

Primary citation

Billas, I.M.L.,Iwema, T.,Garnier, J.M.,Mitschler, A.,Rochel, N.,Moras, D.
Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor.
Nature, 426:91-96, 2003

PubMed 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.

PubMed: 14595375
DOI: 10.1038/nature02112

Experimental method

X-RAY DIFFRACTION (3 Å)