3KMR

Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment

3KMR の概要

• エントリーDOI: 10.2210/pdb3kmr/pdb
• 分子名称: Retinoic acid receptor alpha, Nuclear receptor coactivator 1, 4-{[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl]amino}benzoic acid, ... (4 entities in total)
• 機能のキーワード: nuclear receptor transcription factor ligand binding domain, dna-binding, metal-binding, nucleus, phosphoprotein, proto-oncogene, receptor, transcription, transcription regulation, zinc-finger, activator, acyltransferase, isopeptide bond, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P10276; Nucleus (By similarity): Q15788
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31910.91

構造登録者

Bourguet, W.,Teyssier, C. (登録日: 2009-11-11, 公開日: 2010-06-02, 最終更新日: 2023-09-06)

主引用文献

le Maire, A.,Teyssier, C.,Erb, C.,Grimaldi, M.,Alvarez, S.,de Lera, A.R.,Balaguer, P.,Gronemeyer, H.,Royer, C.A.,Germain, P.,Bourguet, W.
A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor.
Nat.Struct.Mol.Biol., 17:801-807, 2010

PubMed Abstract: In the absence of ligand, some nuclear receptors, including retinoic acid receptor (RAR), act as transcriptional repressors by recruiting corepressor complexes to target genes. This constitutive repression is crucial in metazoan reproduction, development and homeostasis. However, its specific molecular determinants had remained obscure. Using structural, biochemical and cell-based assays, we show that the basal repressive activity of RAR is conferred by an extended beta-strand that forms an antiparallel beta-sheet with specific corepressor residues. Agonist binding induces a beta-strand-to-alpha-helix transition that allows for helix H11 formation, which in turn provokes corepressor release, repositioning of helix H12 and coactivator recruitment. Several lines of evidence suggest that this structural switch could be implicated in the intrinsic repressor function of other nuclear receptors. Finally, we report on the molecular mechanism by which inverse agonists strengthen corepressor interaction and enhance gene silencing by RAR.

PubMed: 20543827
DOI: 10.1038/nsmb.1855

実験手法

X-RAY DIFFRACTION (1.8 Å)