1P93

CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR

1P93 の概要

• エントリーDOI: 10.2210/pdb1p93/pdb
• 関連するPDBエントリー: 1NHZ
• 分子名称: Glucocorticoid receptor, Nuclear receptor coactivator 2, DEXAMETHASONE (3 entities in total)
• 機能のキーワード: protein-ligand complex, anti parallel alpha helix sandwich, hormone receptor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 136105.16

構造登録者

Kauppi, B.,Jakob, C.,Farnegardh, M.,Yang, J.,Ahola, H.,Alarcon, M.,Calles, K.,Engstrom, O.,Harlan, J.,Muchmore, S.,Ramqvist, A.-K.,Thorell, S.,Ohman, L.,Greer, J.,Gustafsson, J.-A.,Carlstedt-Duke, J.,Carlquist, M. (登録日: 2003-05-09, 公開日: 2003-07-08, 最終更新日: 2023-08-16)

主引用文献

Kauppi, B.,Jakob, C.,Farnegardh, M.,Yang, J.,Ahola, H.,Alarcon, M.,Calles, K.,Engstrom, O.,Harlan, J.,Muchmore, S.,Ramqvist, A.-K.,Thorell, S.,Ohman, L.,Greer, J.,Gustafsson, J.-A.,Carlstedt-Duke, J.,Carlquist, M.
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.
J.Biol.Chem., 278:22748-22754, 2003

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

PubMed: 12686538
DOI: 10.1074/jbc.M212711200

実験手法

X-RAY DIFFRACTION (2.7 Å)