3CJW

Crystal structure of the human COUP-TFII ligand binding domain

Summary for 3CJW

• Entry DOI: 10.2210/pdb3cjw/pdb
• Descriptor: COUP transcription factor 2 (1 entity in total)
• Functional Keywords: coup-tfii, nuclear receptor, ligand binding domain, orphan receptor, three-layered helical sandwich, dna-binding, metal-binding, nucleus, receptor, transcription, transcription regulation, zinc, zinc-finger
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 27311.56

Authors

Kruse, S.W.,Reynolds, R.,Vonrhein, C.,Xu, H.E. (deposition date: 2008-03-14, release date: 2008-10-07, Last modification date: 2024-02-21)

Primary citation

Kruse, S.W.,Suino-Powell, K.,Zhou, X.E.,Kretschman, J.E.,Reynolds, R.,Vonrhein, C.,Xu, Y.,Wang, L.,Tsai, S.Y.,Tsai, M.J.,Xu, H.E.
Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid-Activated Receptor.
Plos Biol., 6:e227-e227, 2008

PubMed Abstract: The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 A crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix alpha10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site, thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation.

PubMed: 18798693
DOI: 10.1371/journal.pbio.0060227

Experimental method

X-RAY DIFFRACTION (1.48 Å)