spacer
spacer

PDBsum entry 3a9e

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transcription PDB id
3a9e
Jmol
Contents
Protein chains
218 a.a. *
239 a.a. *
11 a.a. *
Ligands
754
REA
Waters ×115
* Residue conservation analysis
PDB id:
3a9e
Name: Transcription
Title: Crystal structure of a mixed agonist-bound rar-alpha and ant bound rxr-alpha heterodimer ligand binding domains
Structure: Retinoic acid receptor rxr-alpha. Chain: a. Fragment: ligand binding domain. Synonym: retinoid x receptor alpha, nuclear receptor subfam group b member 1. Engineered: yes. Retinoic acid receptor alpha. Chain: b. Fragment: ligand binding domain.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: rxra, nr2b1. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
2.75Å     R-factor:   0.204     R-free:   0.264
Authors: Y.Sato,S.Duclaud,C.Peluso-Iltis,P.Poussin,D.Moras,N.Rochel
Key ref: Y.Sato et al. (2010). The "Phantom Effect" of the Rexinoid LG100754: structural and functional insights. PLoS One, 5, e15119. PubMed id: 21152046
Date:
24-Oct-09     Release date:   06-Oct-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28700  (RXRA_MOUSE) -  Retinoic acid receptor RXR-alpha
Seq:
Struc:
467 a.a.
218 a.a.
Protein chain
Pfam   ArchSchema ?
P10276  (RARA_HUMAN) -  Retinoic acid receptor alpha
Seq:
Struc:
462 a.a.
239 a.a.
Protein chain
Pfam   ArchSchema ?
Q15596  (NCOA2_HUMAN) -  Nuclear receptor coactivator 2
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1464 a.a.
11 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   3 terms 
  Biochemical function     DNA binding     6 terms  

 

 
PLoS One 5:e15119 (2010)
PubMed id: 21152046  
 
 
The "Phantom Effect" of the Rexinoid LG100754: structural and functional insights.
Y.Sato, N.Ramalanjaona, T.Huet, N.Potier, J.Osz, P.Antony, C.Peluso-Iltis, P.Poussin-Courmontagne, E.Ennifar, Y.Mély, A.Dejaegere, D.Moras, N.Rochel.
 
  ABSTRACT  
 
Retinoic acid receptors (RARs) and Retinoid X nuclear receptors (RXRs) are ligand-dependent transcriptional modulators that execute their biological action through the generation of functional heterodimers. RXR acts as an obligate dimer partner in many signalling pathways, gene regulation by rexinoids depending on the liganded state of the specific heterodimeric partner. To address the question of the effect of rexinoid antagonists on RAR/RXR function, we solved the crystal structure of the heterodimer formed by the ligand binding domain (LBD) of the RARα bound to its natural agonist ligand (all-trans retinoic acid, atRA) and RXRα bound to a rexinoid antagonist (LG100754). We observed that RARα exhibits the canonical agonist conformation and RXRα an antagonist one with the C-terminal H12 flipping out to the solvent. Examination of the protein-LG100754 interactions reveals that its propoxy group sterically prevents the H12 associating with the LBD, without affecting the dimerization or the active conformation of RAR. Although LG100754 has been reported to act as a 'phantom ligand' activating RAR in a cellular context, our structural data and biochemical assays demonstrate that LG100754 mediates its effect as a full RXR antagonist. Finally we show that the 'phantom ligand effect' of the LG100754 is due to a direct binding of the ligand to RAR that stabilizes coactivator interactions thus accounting for the observed transcriptional activation of RAR/RXR.