The Three-dimensional Structures of Antagonistic and Agonistic Forms of the Glucocorticoid Receptor Ligand-binding Domain RU-486 INDUCES A TRANSCONFORMATION THAT LEADS TO ACTIVE ANTAGONISM

摘要: Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with antagonist RU-486 at 2.3 A resolution and agonist dexamethasone ligand together a coactivator peptide 2.8 A. The structure was solved several different forms, two helix 12 intact (GR1 GR3) one protease-digested C terminus (GR2). In GR1, part is position that covers co-activator pocket, whereas GR3, swapping seen between crystallographically identical subunits GR dimer. An arm consisting end 11 beyond stretches out from molecule, binds to other LBD, partly blocking pocket molecule. This type GR-LBD dimer has not been described before but might be an artifact crystallization. Furthermore, GR3 dimers are covalently connected via disulfide bond Cys-736 residues molecules. All three show very flexible region 12.