Ren Bin, Peat Thomas S, Streltsov Victor A, Pollard Matthew, Fernley Ross, Grusovin Julian, Seabrook Shane, Pilling Pat, Phan Tram, Lu Louis, Lovrecz George O, Graham Lloyd D, Hill Ronald J
CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
CSIRO Animal, Food and Health Sciences, PO Box 52, North Ryde, NSW 1670, Australia.
Acta Crystallogr D Biol Crystallogr. 2014 Jul;70(Pt 7):1954-64. doi: 10.1107/S1399004714009626. Epub 2014 Jun 29.
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.
绵羊虱（Bovicola ovis）蜕皮激素受体的异二聚体配体结合区域已在蜕皮甾体或合成亚甲基内酰胺杀虫剂存在的情况下结晶。在2.7 Å分辨率下测定的两个X射线晶体结构表明，该受体两个亚基的配体结合结构域与其他核受体的配体结合结构域一样，可表现出显著的构象灵活性。热熔实验表明，虽然蜕皮甾酮A可稳定溶液中异二聚体的高级结构，但亚甲基内酰胺会使其不稳定。在亚甲基内酰胺存在下结晶的结构中观察到的EcR和USP亚基的构象，在任何蜕皮激素受体结构中均未见过，代表了这些重要受体构象灵活性的新水平。有趣的是，新的USP构象呈现出一个开放的、未占据的配体结合口袋。
