title: Unprecedented conformational flexibility revealed in the ligand-binding domains of the Bovicola ovis ecdysone receptor (EcR) and ultraspiracle (USP) subunits.
abstract: The heterodimeric ligand-binding region of the Bovicola ovis ecdysone receptor has been crystallized either in the presence of an ecdysteroid or a synthetic methylene lactam insecticide. Two X-ray crystallographic structures, determined at 2.7 Å resolution, show that the ligand-binding domains of both subunits of this receptor, like those of other nuclear receptors, can display significant conformational flexibility. Thermal melt experiments show that while ponasterone A stabilizes the higher order structure of the heterodimer in solution, the methylene lactam destabilizes it. The conformations of the EcR and USP subunits observed in the structure crystallized in the presence of the methylene lactam have not been seen previously in any ecdysone receptor structure and represent a new level of conformational flexibility for these important receptors. Interestingly, the new USP conformation presents an open, unoccupied ligand-binding pocket.
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Bin
authors.initials: B
authors.lastname: Ren
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Peat
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Streltsov
authors.affiliation: CSIRO Animal, Food and Health Sciences, PO Box 52, North Ryde, NSW 1670, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pollard
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Fernley
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Grusovin
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Shane
authors.initials: S
authors.lastname: Seabrook
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Pat
authors.initials: P
authors.lastname: Pilling
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Tram
authors.initials: T
authors.lastname: Phan
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Louis
authors.initials: L
authors.lastname: Lu
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: George O
authors.initials: GO
authors.lastname: Lovrecz
authors.affiliation: CSIRO Animal, Food and Health Sciences, PO Box 52, North Ryde, NSW 1670, Australia.
authors.forename: Lloyd D
authors.initials: LD
authors.lastname: Graham
authors.affiliation: CSIRO Animal, Food and Health Sciences, PO Box 52, North Ryde, NSW 1670, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hill
mesh_terms: D000818:Animals; D058326:Ischnocera / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D011987:Receptors, Steroid; C055469:ecdysone receptor
keywords: Bovicola ovis; ecdysone receptor; ultraspiracle