3P0U

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

Summary for 3P0U

• Entry DOI: 10.2210/pdb3p0u/pdb
• Descriptor: Nuclear receptor subfamily 2 group C member 2 (2 entities in total)
• Functional Keywords: ligand binding domain, orphan nuclear receptor, testicular receptor 4, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P49116
• Total number of polymer chains: 2
• Total formula weight: 56204.38

Authors

Zhou, X.E.,Suino-Powell, K.M.,Xu, Y.,Chan, C.-W.,Kruse, S.W.,Reynolds, R.,Engel, J.D.,Xu, H.E. (deposition date: 2010-09-29, release date: 2010-11-10, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)