The Structure and Function of Ecdysone Receptors

Abstract

The ligand-binding properties of recombinant ecdysone receptor EcR-USP heterodimeric ligand-binding domains (LBDs) from four insect orders are described for a range of ecdysteroids and for a dibenzoylhydrazine (DBH) insecticide (tebufenozide). Much of the order selectivity of the insecticide in the field is reproduced by the affinity of tebufenozide for the recombinant LBDs in the laboratory. Crystal structures are presented for the LBDs of ecdysone receptors from the pest insects Heliothis virescens, Bemisia tabaci and Tribolium castaneum in complex with ponasterone A, as well as of the H. virescens LBD in complex with 20-hydroxyecdysone and BYI06830 (a DBH insecticide). Comparison of ecdysteroid-and BYI06830-bound structures of the H. virescens LBD illustrates the way in which this remarkable protein can adapt its binding pocket to very different ligand chemistries. Finally, comparison of the ligand-binding pockets of H. virescens, B. tabaci and T. castaneum ecdysone receptors begins to provide insights at an atomic level of detail into the insect order selectivity of the DBH insecticides. Keywords Ecdysone receptor • ligand binding domain • 20-hydroxyecdysone • ponasterone A • tebufenozide • dibenzoylhydrazine • X-ray crystal structure