3P0U

Crystal Structure of the ligand binding domain of human testicular receptor 4

3P0U の概要

• エントリーDOI: 10.2210/pdb3p0u/pdb
• 分子名称: Nuclear receptor subfamily 2 group C member 2 (2 entities in total)
• 機能のキーワード: ligand binding domain, orphan nuclear receptor, testicular receptor 4, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P49116
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56204.38

構造登録者

Zhou, X.E.,Suino-Powell, K.M.,Xu, Y.,Chan, C.-W.,Kruse, S.W.,Reynolds, R.,Engel, J.D.,Xu, H.E. (登録日: 2010-09-29, 公開日: 2010-11-10, 最終更新日: 2024-02-21)

主引用文献

Zhou, X.E.,Suino-Powell, K.M.,Xu, Y.,Chan, C.W.,Tanabe, O.,Kruse, S.W.,Reynolds, R.,Engel, J.D.,Xu, H.E.
The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor.
J.Biol.Chem., 286:2877-2885, 2011

PubMed Abstract: Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

PubMed: 21068381
DOI: 10.1074/jbc.M110.168740

実験手法

X-RAY DIFFRACTION (3 Å)