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PDBsum entry 2v0v

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protein Protein-protein interface(s) links
Transcription PDB id
2v0v
Jmol
Contents
Protein chain
181 a.a. *
Waters ×96
* Residue conservation analysis
PDB id:
2v0v
Name: Transcription
Title: Crystal structure of rev-erb beta
Structure: Orphan nuclear receptor nr1d2. Chain: a, b, c, d. Fragment: ligand-binding domain, residues 386-579. Synonym: ear-1r, orphan nuclear hormone receptor bd73, rev-erb beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Resolution:
2.40Å     R-factor:   0.137     R-free:   0.219
Authors: E.-J.Woo,D.G.Jeong,M.-Y.Lim,S.Jun Kim,S.Eon Ryu
Key ref:
E.J.Woo et al. (2007). Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta. J Mol Biol, 373, 735-744. PubMed id: 17870090 DOI: 10.1016/j.jmb.2007.08.037
Date:
19-May-07     Release date:   23-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q14995  (NR1D2_HUMAN) -  Nuclear receptor subfamily 1 group D member 2
Seq:
Struc:
 
Seq:
Struc:
579 a.a.
181 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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  

 

 
DOI no: 10.1016/j.jmb.2007.08.037 J Mol Biol 373:735-744 (2007)
PubMed id: 17870090  
 
 
Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta.
E.J.Woo, D.G.Jeong, M.Y.Lim, S.Jun Kim, K.J.Kim, S.M.Yoon, B.C.Park, S.Eon Ryu.
 
  ABSTRACT  
 
The Rev-erb family is an orphan nuclear receptor acting as a negative regulator of transcription. Rev-erbalpha and Rev-erbbeta are crucial components of the circadian clock and involved in various lipid homeostasis. They are unique nuclear receptors that lack the activation function 2 helix (AF2-helix) required for ligand-dependent activation by other members of nuclear receptors. Here, we report the crystal structure of Rev-erbbeta (NR1D2) in a dimeric arrangement. The putative ligand-binding pocket (LBP) of Rev-erbbeta is filled with bulky hydrophobic residues resulting in a residual cavity size that is too small to allow binding of any known ligand molecules. However, an alternative conformation of the putative LBP observed in another crystal form suggests the flexibility of this region. The kinked conformation of helix H11 allows helix H11 to bend toward helix H3 over the putative ligand binding pocket by filling and closing the cavity with its side-chains. In the absence of the AF2-helix and a cognate ligand, Rev-erbbeta appears to stabilize the hydrophobic cluster in the putative ligand binding pocket and provide a structural platform for co-repressor binding by adopting the unique geometry of helix H11, a suitable conformation for the constitutive repression activity.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall structure of human Rev-erbβ LBD. (a) Schematic overview of the Rev-erbβ dimer with the 2-fold axis in a vertical orientation (left) and in a horizontal orientation, perpendicular to the plane (right). Each monomer is colored blue and green with the helix H11 colored red. (b) Stereo view of the superposition of the C^α traces of the Rev-erbβ (blue) monomer and the RARγ (red) monomer. A region of the amino aacid residues 182–218 of RARγ is omitted from the Figure for clarity. (c) Superposition of the structure of Rev-erbβ LBD (blue) onto the RARγ LBD (cyan), represented in solid rendering (α helices in cylinders and β strands in arrows). The different regions between the two LBDs correspond to the tilt of the N termini of H3 and H7 toward the center of the LBP and the lid-like conformation of H11 (pink). The ligand, all-trans retinoic acid, bound to RARγ is shown using orange spheres.
Figure 4.
Figure 4. Model structures of NCoR1 peptides, ID-I and ID-II, bound to Rev-erbβ. (a) Residues comprising the surface groove of Rev-erbβ and those involved in binding to the NCOR1 peptide ID-I are drawn using green sticks. Co-repressor peptide ID-I is colored orange with some side-chains drawn as sticks except for F575 Residues F409, L572, F405 and F575 buried in the hydrophobic cluster are shown in blue. (b) Co-repressor peptide ID-II, interacting to the same groove as ID-I, is colored orange with some side-chains drawn as sticks. The surface groove is shown with residues (green) that affected the binding to NCoR1 in previous mutational studies. Some residues lining the groove are labeled. Helix H11 is highlighted in red.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 373, 735-744) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20581824 C.A.Phelan, R.T.Gampe, M.H.Lambert, D.J.Parks, V.Montana, J.Bynum, T.M.Broderick, X.Hu, S.P.Williams, R.T.Nolte, and M.A.Lazar (2010).
Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction.
  Nat Struct Mol Biol, 17, 808-814.
PDB code: 3n00
20159955 I.Schmutz, J.A.Ripperger, S.Baeriswyl-Aebischer, and U.Albrecht (2010).
The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors.
  Genes Dev, 24, 345-357.  
20723571 L.Jin, and Y.Li (2010).
Structural and functional insights into nuclear receptor signaling.
  Adv Drug Deliv Rev, 62, 1218-1226.  
20148675 P.Huang, V.Chandra, and F.Rastinejad (2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
  Annu Rev Physiol, 72, 247-272.  
19582836 G.Wohlfahrt, J.Sipilä, and L.O.Pietilä (2009).
Field-based comparison of ligand and coactivator binding sites of nuclear receptors.
  Biopolymers, 91, 884-894.  
19405475 K.A.Marvin, J.L.Reinking, A.J.Lee, K.Pardee, H.M.Krause, and J.N.Burstyn (2009).
Nuclear receptors homo sapiens Rev-erbbeta and Drosophila melanogaster E75 are thiolate-ligated heme proteins which undergo redox-mediated ligand switching and bind CO and NO.
  Biochemistry, 48, 7056-7071.  
19243223 K.I.Pardee, X.Xu, J.Reinking, A.Schuetz, A.Dong, S.Liu, R.Zhang, J.Tiefenbach, G.Lajoie, A.N.Plotnikov, A.Botchkarev, H.M.Krause, and A.Edwards (2009).
The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta.
  PLoS Biol, 7, e43.
PDB code: 3cqv
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.