PDBsum entry 3e94

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Transcription PDB id
Protein chain
211 a.a. *
Waters ×160
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of rxralpha ligand binding domain in complex with tributyltin and a coactivator fragment
Structure: Retinoic acid receptor rxr-alpha. Chain: a. Fragment: ligand binding domain (unp residues 223-462). Synonym: retinoid x receptor alpha, nuclear receptor subfamily 2 group b member 1. Engineered: yes. Nuclear receptor coactivator 2 peptide. Chain: b. Fragment: nuclear receptor box 2 (unp residues 686-698).
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: rxra, nr2b1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence can be naturally found in homo sapiens (human).
1.90Å     R-factor:   0.192     R-free:   0.225
Authors: W.Bourguet,A.Le Maire
Key ref: A.le Maire et al. (2009). Activation of RXR-PPAR heterodimers by organotin environmental endocrine disruptors. EMBO Rep, 10, 367-373. PubMed id: 19270714
21-Aug-08     Release date:   10-Mar-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P19793  (RXRA_HUMAN) -  Retinoic acid receptor RXR-alpha
462 a.a.
211 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  


EMBO Rep 10:367-373 (2009)
PubMed id: 19270714  
Activation of RXR-PPAR heterodimers by organotin environmental endocrine disruptors.
A.le Maire, M.Grimaldi, D.Roecklin, S.Dagnino, V.Vivat-Hannah, P.Balaguer, W.Bourguet.
The nuclear receptor retinoid X receptor-alpha (RXR-alpha)-peroxisome proliferator-activated receptor-gamma (PPAR-gamma) heterodimer was recently reported to have a crucial function in mediating the deleterious effects of organotin compounds, which are ubiquitous environmental contaminants. However, because organotins are unrelated to known RXR-alpha and PPAR-gamma ligands, the mechanism by which these compounds bind to and activate the RXR-alpha-PPAR-gamma heterodimer at nanomolar concentrations has remained elusive. Here, we show that tributyltin (TBT) activates all three RXR-PPAR-alpha, -gamma, -delta heterodimers, primarily through its interaction with RXR. In addition, the 1.9 A resolution structure of the RXR-alpha ligand-binding domain in complex with TBT shows a covalent bond between the tin atom and residue Cys 432 of helix H11. This interaction largely accounts for the high binding affinity of TBT, which only partly occupies the RXR-alpha ligand-binding pocket. Our data allow an understanding of the binding and activation properties of the various organotins and suggest a mechanism by which these tin compounds could affect other nuclear receptor signalling pathways.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21425440 A.Janesick, and B.Blumberg (2011).
Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity.
  Birth Defects Res C Embryo Today, 93, 34-50.  
21054169 C.Casals-Casas, and B.Desvergne (2011).
Endocrine disruptors: from endocrine to metabolic disruption.
  Annu Rev Physiol, 73, 135-162.  
21354421 Y.Verhaegen, K.Parmentier, L.Swevers, E.Renders, P.Rougé, W.De Coen, K.Cooreman, and G.Smagghe (2011).
The heterodimeric ecdysteroid receptor complex in the brown shrimp Crangon crangon: EcR and RXR isoform characteristics and sensitivity towards the marine pollutant tributyltin.
  Gen Comp Endocrinol, 172, 158-169.  
  20056577 A.Suvorov, and L.Takser (2010).
Global gene expression analysis in the livers of rat offspring perinatally exposed to low doses of 2,2',4,4'-tetrabromodiphenyl ether.
  Environ Health Perspect, 118, 97.  
20063036 A.le Maire, W.Bourguet, and P.Balaguer (2010).
A structural view of nuclear hormone receptor: endocrine disruptor interactions.
  Cell Mol Life Sci, 67, 1219-1237.
PDB code: 3kwy
20689419 F.Grün (2010).
  Curr Opin Endocrinol Diabetes Obes, 17, 453-459.  
20674387 P.Lefebvre, Y.Benomar, and B.Staels (2010).
Retinoid X receptors: common heterodimerization partners with distinct functions.
  Trends Endocrinol Metab, 21, 676-683.  
19960246 T.Horiguchi, H.Urushitani, Y.Ohta, T.Iguchi, and H.Shiraishi (2010).
Establishment of a polyclonal antibody against the retinoid X receptor of the rock shell Thais clavigera and its application to rock shell tissues for imposex research.
  Ecotoxicology, 19, 571-576.  
20033144 W.Mnif, S.Dagnino, A.Escande, A.Pillon, H.Fenet, E.Gomez, C.Casellas, M.J.Duchesne, G.Hernandez-Raquet, V.Cavaillès, P.Balaguer, and A.Bartegi (2010).
Biological analysis of endocrine-disrupting compounds in Tunisian sewage treatment plants.
  Arch Environ Contam Toxicol, 59, 1.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.