4PP6

Crystal Structure of the Estrogen Receptor alpha Ligand-binding Domain in Complex with Resveratrol

4PP6 の概要

• エントリーDOI: 10.2210/pdb4pp6/pdb
• 関連するPDBエントリー: 4PPP 4PPS
• 分子名称: Estrogen receptor, Nuclear receptor coactivator 2, RESVERATROL, ... (4 entities in total)
• 機能のキーワード: nuclear hormone receptor, transcription factor, ligand binding, nucleus, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Isoform 1: Nucleus. Isoform 3: Nucleus. Nucleus: P03372; Nucleus: Q15596
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 58398.82

構造登録者

Nwachukwu, J.C.,Srinivasan, S.,Bruno, N.E.,Parent, A.A.,Hughes, T.S.,Pollock, J.A.,Gjyshi, O.,Cavett, V.,Nowak, J.,Garcia-Ordonez, R.D.,Houtman, R.,Griffin, P.R.,Kojetin, D.J.,Katzenellenbogen, J.A.,Conkright, M.D.,Nettles, K.W. (登録日: 2014-02-26, 公開日: 2014-05-07, 最終更新日: 2023-09-20)

主引用文献

Nwachukwu, J.C.,Srinivasan, S.,Bruno, N.E.,Parent, A.A.,Hughes, T.S.,Pollock, J.A.,Gjyshi, O.,Cavett, V.,Nowak, J.,Garcia-Ordonez, R.D.,Houtman, R.,Griffin, P.R.,Kojetin, D.J.,Katzenellenbogen, J.A.,Conkright, M.D.,Nettles, K.W.
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.
Elife, 3:e02057-e02057, 2014

PubMed Abstract: Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity.DOI: http://dx.doi.org/10.7554/eLife.02057.001.

PubMed: 24771768
DOI: 10.7554/eLife.02057

実験手法

X-RAY DIFFRACTION (2.201 Å)