3H52

Crystal structure of the antagonist form of human glucocorticoid receptor

3H52 の概要

• エントリーDOI: 10.2210/pdb3h52/pdb
• 分子名称: Glucocorticoid receptor, Nuclear receptor corepressor 1, 11-(4-DIMETHYLAMINO-PHENYL)-17-HYDROXY-13-METHYL-17-PROP-1-YNYL-1,2,6,7,8,11,12,13,14,15,16,17-DODEC AHYDRO-CYCLOPENTA[A]PHENANTHREN-3-ONE, ... (5 entities in total)
• 機能のキーワード: protein-ligand complex, nuclear receptor, peptide complex, hormone receptor 3, hormone receptor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm. Isoform Beta: Nucleus: P04150; Nucleus (By similarity): O75376
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 123175.56

構造登録者

Schoch, G.A.,Benz, J.,D'Arcy, B.,Stihle, M.,Burger, D.,Thoma, R.,Ruf, A. (登録日: 2009-04-21, 公開日: 2009-12-01, 最終更新日: 2023-11-01)

主引用文献

Schoch, G.A.,D'Arcy, B.,Stihle, M.,Burger, D.,Bar, D.,Benz, J.,Thoma, R.,Ruf, A.
Molecular switch in the glucocorticoid receptor: active and passive antagonist conformations
J.Mol.Biol., 395:568-577, 2010

PubMed Abstract: Mifepristone is known to induce mixed passive antagonist, active antagonist, and agonist effects via the glucocorticoid receptor (GR) pathway. Part of the antagonist effects of mifepristone are due to the repression of gene transcription mediated by the nuclear receptor corepressor (NCoR). Here, we report the crystal structure of a ternary complex of the GR ligand binding domain (GR-LBD) with mifepristone and a receptor-interacting motif of NCoR. The structures of three different conformations of the GR-LBD mifepristone complex show in the oxosteroid hormone receptor family how helix 12 modulates LBD corepressor and coactivator binding. Differences in NCoR binding and in helix 12 conformation reveal how the 11beta substituent in mifepristone triggers the helix 12 molecular switch to reshape the coactivator site into the corepressor site. Two observed conformations exemplify the active antagonist state of GR with NCoR bound. In another conformation, helix 12 completely blocks the coregulator binding site and explains the passive antagonistic effect of mifepristone on GR.

PubMed: 19913032
DOI: 10.1016/j.jmb.2009.11.011

実験手法

X-RAY DIFFRACTION (2.8 Å)