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PDBsum entry 3dzu

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protein dna_rna ligands metals Protein-protein interface(s) links
Transcription/DNA PDB id
3dzu
Jmol
Contents
Protein chains
289 a.a. *
359 a.a. *
DNA/RNA
Ligands
LYS-ILE-LEU-HIS-
ARG-LEU-LEU-GLN-
ASP
LYS-ILE-LEU-HIS-
ARG-LEU-LEU-GLN
REA
PLB
Metals
_ZN ×4
* Residue conservation analysis
PDB id:
3dzu
Name: Transcription/DNA
Title: Intact ppar gamma - rxr alpha nuclear receptor complex on dn with bvt.13, 9-cis retinoic acid and ncoa2 peptide
Structure: Retinoic acid receptor rxr-alpha. Chain: a. Fragment: unp residues 11-462. Synonym: retinoid x receptor alpha, nuclear receptor subfam group b member 1. Engineered: yes. Peroxisome proliferator-activated receptor gamma. Chain: d. Fragment: unp residues 102-505.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: rxra, nr2b1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: pparg, nr1c3. Synthetic: yes. Other_details: synthetic DNA.
Resolution:
3.20Å     R-factor:   0.201     R-free:   0.272
Authors: V.Chandra,P.Huang,Y.Hamuro,S.Raghuram,Y.Wang,T.P.Burris,F.Ra
Key ref: V.Chandra et al. (2008). Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature, 456, 350-356. PubMed id: 19043829
Date:
30-Jul-08     Release date:   28-Oct-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P19793  (RXRA_HUMAN) -  Retinoic acid receptor RXR-alpha
Seq:
Struc:
462 a.a.
289 a.a.
Protein chain
Pfam   ArchSchema ?
P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma
Seq:
Struc:
505 a.a.
359 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   3 terms 
  Biological process     viral reproduction   30 terms 
  Biochemical function     RNA polymerase II regulatory region sequence-specific DNA binding     20 terms  

 

 
Nature 456:350-356 (2008)
PubMed id: 19043829  
 
 
Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA.
V.Chandra, P.Huang, Y.Hamuro, S.Raghuram, Y.Wang, T.P.Burris, F.Rastinejad.
 
  ABSTRACT  
 
Nuclear receptors are multi-domain transcription factors that bind to DNA elements from which they regulate gene expression. The peroxisome proliferator-activated receptors (PPARs) form heterodimers with the retinoid X receptor (RXR), and PPAR-gamma has been intensively studied as a drug target because of its link to insulin sensitization. Previous structural studies have focused on isolated DNA or ligand-binding segments, with no demonstration of how multiple domains cooperate to modulate receptor properties. Here we present structures of intact PPAR-gamma and RXR-alpha as a heterodimer bound to DNA, ligands and coactivator peptides. PPAR-gamma and RXR-alpha form a non-symmetric complex, allowing the ligand-binding domain (LBD) of PPAR-gamma to contact multiple domains in both proteins. Three interfaces link PPAR-gamma and RXR-alpha, including some that are DNA dependent. The PPAR-gamma LBD cooperates with both DNA-binding domains (DBDs) to enhance response-element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene-activation properties.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21478866 J.Zhang, M.J.Chalmers, K.R.Stayrook, L.L.Burris, Y.Wang, S.A.Busby, B.D.Pascal, R.D.Garcia-Ordonez, J.B.Bruning, M.A.Istrate, D.J.Kojetin, J.A.Dodge, T.P.Burris, and P.R.Griffin (2011).
DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex.
  Nat Struct Mol Biol, 18, 556-563.  
21478865 N.Rochel, F.Ciesielski, J.Godet, E.Moman, M.Roessle, C.Peluso-Iltis, M.Moulin, M.Haertlein, P.Callow, Y.Mély, D.I.Svergun, and D.Moras (2011).
Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings.
  Nat Struct Mol Biol, 18, 564-570.  
20657587 D.Kim, B.J.Blus, V.Chandra, P.Huang, F.Rastinejad, and S.Khorasanizadeh (2010).
Corecognition of DNA and a methylated histone tail by the MSL3 chromodomain.
  Nat Struct Mol Biol, 17, 1027-1029.
PDB codes: 3m9p 3m9q 3oa6
19487700 M.L.Privalsky, S.Lee, J.B.Hahm, B.M.Young, R.N.Fong, and I.H.Chan (2009).
The p160 coactivator PAS-B motif stabilizes nuclear receptor binding and contributes to isoform-specific regulation by thyroid hormone receptors.
  J Biol Chem, 284, 19554-19563.  
19622862 T.Oyama, K.Toyota, T.Waku, Y.Hirakawa, N.Nagasawa, J.I.Kasuga, Y.Hashimoto, H.Miyachi, and K.Morikawa (2009).
Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures.
  Acta Crystallogr D Biol Crystallogr, 65, 786-795.
PDB codes: 2znn 2zno 2znp 2znq
19888307 Y.Pan, C.J.Tsai, B.Ma, and R.Nussinov (2009).
How do transcription factors select specific binding sites in the genome?
  Nat Struct Mol Biol, 16, 1118-1120.  
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 codes are shown on the right.