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PDBsum entry 3kmz

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protein ligands Protein-protein interface(s) links
Transcription PDB id
3kmz
Jmol
Contents
Protein chains
221 a.a. *
19 a.a. *
Ligands
EQO ×2
GOL ×9
Waters ×298
* Residue conservation analysis
PDB id:
3kmz
Name: Transcription
Title: Crystal structure of raralpha ligand binding domain in compl the inverse agonist bms493 and a corepressor fragment
Structure: Retinoic acid receptor alpha. Chain: b, a. Fragment: ligand binding domain. Synonym: rar-alpha, nuclear receptor subfamily 1 group b me engineered: yes. Nuclear receptor corepressor 1. Chain: c, d. Fragment: nr1. Synonym: n-cor1, n-cor.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nr1b1, rara. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic
Resolution:
2.10Å     R-factor:   0.175     R-free:   0.230
Authors: W.Bourguet,A.Le Maire
Key ref: A.le Maire et al. (2010). A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor. Nat Struct Mol Biol, 17, 801-807. PubMed id: 20543827
Date:
11-Nov-09     Release date:   02-Jun-10    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P10276  (RARA_HUMAN) -  Retinoic acid receptor alpha
Seq:
Struc:
462 a.a.
221 a.a.
Protein chains
Pfam   ArchSchema ?
O75376  (NCOR1_HUMAN) -  Nuclear receptor corepressor 1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2440 a.a.
19 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     4 terms  

 

 
Nat Struct Mol Biol 17:801-807 (2010)
PubMed id: 20543827  
 
 
A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor.
A.le Maire, C.Teyssier, C.Erb, M.Grimaldi, S.Alvarez, A.R.de Lera, P.Balaguer, H.Gronemeyer, C.A.Royer, P.Germain, W.Bourguet.
 
  ABSTRACT  
 
In the absence of ligand, some nuclear receptors, including retinoic acid receptor (RAR), act as transcriptional repressors by recruiting corepressor complexes to target genes. This constitutive repression is crucial in metazoan reproduction, development and homeostasis. However, its specific molecular determinants had remained obscure. Using structural, biochemical and cell-based assays, we show that the basal repressive activity of RAR is conferred by an extended beta-strand that forms an antiparallel beta-sheet with specific corepressor residues. Agonist binding induces a beta-strand-to-alpha-helix transition that allows for helix H11 formation, which in turn provokes corepressor release, repositioning of helix H12 and coactivator recruitment. Several lines of evidence suggest that this structural switch could be implicated in the intrinsic repressor function of other nuclear receptors. Finally, we report on the molecular mechanism by which inverse agonists strengthen corepressor interaction and enhance gene silencing by RAR.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20836077 L.J.Gudas, and J.A.Wagner (2011).
Retinoids regulate stem cell differentiation.
  J Cell Physiol, 226, 322-330.  
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