3CJW

Crystal structure of the human COUP-TFII ligand binding domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.168 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid-Activated Receptor.

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.

(2008) PLoS Biol 6: e227-e227

  • DOI: https://doi.org/10.1371/journal.pbio.0060227
  • Primary Citation of Related Structures:  
    3CJW

  • 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.


  • Organizational Affiliation

    Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, Michigan, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
COUP transcription factor 2244Homo sapiensMutation(s): 0 
Gene Names: NR2F2ARP1TFCOUP2
UniProt & NIH Common Fund Data Resources
Find proteins for P24468 (Homo sapiens)
Explore P24468 
Go to UniProtKB:  P24468
PHAROS:  P24468
GTEx:  ENSG00000185551 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP24468
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.168 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.854α = 90
b = 47.762β = 100.87
c = 43.128γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-05-06
    Changes: Database references, Derived calculations, Source and taxonomy
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references