PDBsum entry 1a6y

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protein dna_rna metals Protein-protein interface(s) links
Transcription/DNA PDB id
Protein chains
78 a.a. *
84 a.a. *
_ZN ×4
Waters ×234
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Reverba orphan nuclear receptor/DNA complex
Structure: DNA (5'- d( Cp Ap Ap Cp Tp Ap Gp Gp Tp Cp Ap Cp (5It) p Ap Gp Gp Tp Cp Ap G)-3'). Chain: c. Engineered: yes. DNA (5'- d( Cp Tp Gp Ap Cp Cp Tp Ap Gp Tp Gp Ap Cp Cp Tp Ap Gp Tp Tp G)-3'). Chain: d.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Tetramer (from PQS)
2.30Å     R-factor:   0.192     R-free:   0.288
Authors: Q.Zhao,S.Khorasanizadeh,F.Rastinejad
Key ref:
Q.Zhao et al. (1998). Structural elements of an orphan nuclear receptor-DNA complex. Mol Cell, 1, 849-861. PubMed id: 9660968 DOI: 10.1016/S1097-2765(00)80084-2
04-Mar-98     Release date:   21-Oct-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P20393  (NR1D1_HUMAN) -  Nuclear receptor subfamily 1 group D member 1
614 a.a.
78 a.a.*
Protein chain
Pfam   ArchSchema ?
P20393  (NR1D1_HUMAN) -  Nuclear receptor subfamily 1 group D member 1
614 a.a.
84 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     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     DNA binding     6 terms  


DOI no: 10.1016/S1097-2765(00)80084-2 Mol Cell 1:849-861 (1998)
PubMed id: 9660968  
Structural elements of an orphan nuclear receptor-DNA complex.
Q.Zhao, S.Khorasanizadeh, Y.Miyoshi, M.A.Lazar, F.Rastinejad.
The nuclear hormone receptors form the largest known family of transcription factors. The current notion of receptor DNA discrimination, based solely on one major type of hexameric half-site and a highly conserved 66-residue core DNA-binding domain (DBD), does not adequately describe how more than 150 nonsteroid receptors differentiate among response elements. Here, we describe the 2.3 A crystal structure of the DNA-binding region of the orphan receptor RevErb arranged as a tandem homodimer on its optimal response element. The structure reveals the presence of a second major protein-DNA interface adjacent to the classical one involving the half-sites. A sequence comparison of orphan receptors suggests that unique minor-groove interactions involving the receptor hinge regions impart the necessary DNA and dimerization specificity.
  Selected figure(s)  
Figure 1.
Figure 1. The Protein and DNA Constructs Used in Crystallization and Their Contacts(a and b) The upstream (a) and downstream (b) positioned DNA-binding regions of human RevErbα are numbered starting with the first conserved cysteine. The authentic numbers appear in the parentheses. Dashed lines indicate amino- and carboxy-terminal residues not found in the electron density maps. Closed and open arrows indicate direct and water-mediated hydrogen bonds to the DNA bases, respectively. Closed and open boxes indicate direct and water-mediated hydrogen bonds to the DNA phosphates. Colored circles indicate Van der Waals contacts with the DNA, and closed black circles indicate residues that mediate subunit dimerization. A symbol indicates one or more such contacts.(c) The 20 base pair DNA is numbered from the 5′ end, with arrows indicating the half-site repeats and boxes indicating the spacer and 5′ flanking sequence. Shown are the upstream (green) and downstream (red) contacts from the RevErb subunits.
Figure 2.
Figure 2. Overall Architecture of the Complex(a) The overall architecture of the complex. The green polypeptide and the red polypeptides are the upstream and downstream subunits, respectively. Zincs are shown as gray spheres. The conserved AGGTCA half-sites are shown in purple, and the 5′ flanking base pairs and spacer are shown in yellow.(b) Surface representation of the protein–DNA complex. The view is nearly identical to that shown in (a). The location of the Grip box in the minor groove is indicated.(c) Stereo diagram of the overall complex, showing the side chains (in yellow) mediating direct protein–DNA contacts and those coordinating the zinc ions (in pink). The green polypeptide is the upstream subunit. The yellow spheres are zincs, and their coordinating cysteines are in pink. The numbers along the DNA indicate the sequence as shown in Figure 1c.Half-Site Contacts(d and e) Schematic summary of upstream (d) and downstream (e) contacts between the core DBD and the half-sites. Red arrows indicate hydrogen bonding to the DNA phosphates; black arrows indicate other hydrogen bonds. The arrowhead indicates the probable hydrogen-bond acceptor. The contacts involve the side chains, unless otherwise stated. Amino acids in black make at least one direct hydrogen bond to the DNA bases. Residues circled in green make different DNA interactions in the two subunits. The blue circles are water molecules that mediate protein–DNA contacts. The yellow base pairs are different in steroid-receptor response elements. The DNA shown is underwound for clarity.
  The above figures are reprinted by permission from Cell Press: Mol Cell (1998, 1, 849-861) copyright 1998.  
  Figures were selected by an automated process.  

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.  
20414452 L.Yin, N.Wu, and M.A.Lazar (2010).
Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism.
  Nucl Recept Signal, 8, e001.  
20551177 M.Stratmann, F.Stadler, F.Tamanini, G.T.van der Horst, and J.A.Ripperger (2010).
Flexible phase adjustment of circadian albumin D site-binding protein (DBP) gene expression by CRYPTOCHROME1.
  Genes Dev, 24, 1317-1328.  
20530906 W.Li, Y.Yuan, Z.Luo, X.Zheng, L.Zhao, W.Duan, and Y.Yu (2010).
Bacterial expression, refolding, functional characterization, and mass spectrometric identification of full-length human PPAR-gamma.
  Biosci Biotechnol Biochem, 74, 1173-1180.  
19553667 K.K.Hill, S.C.Roemer, D.N.Jones, M.E.Churchill, and D.P.Edwards (2009).
A progesterone receptor co-activator (JDP2) mediates activity through interaction with residues in the carboxyl-terminal extension of the DNA binding domain.
  J Biol Chem, 284, 24415-24424.  
19823680 R.Roduit, P.Escher, and D.F.Schorderet (2009).
Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX.
  PLoS One, 4, e7379.  
18829458 P.Lu, G.B.Rha, M.Melikishvili, G.Wu, B.C.Adkins, M.G.Fried, and Y.I.Chi (2008).
Structural Basis of Natural Promoter Recognition by a Unique Nuclear Receptor, HNF4{alpha}: DIABETES GENE PRODUCT.
  J Biol Chem, 283, 33685-33697.
PDB code: 3cbb
18474528 S.C.Roemer, J.Adelman, M.E.Churchill, and D.P.Edwards (2008).
Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding.
  Nucleic Acids Res, 36, 3655-3666.  
18049881 T.Krusiński, M.Wietrzych, I.Grad, A.Ozyhar, and P.Dobryszycki (2008).
Equilibrium Analysis of the DNA Binding Domain of the Ultraspiracle Protein Interaction with the Response Element from the hsp27 Gene Promoter-the Application of Molecular Beacon Technology.
  J Fluoresc, 18, 1.  
19043829 V.Chandra, P.Huang, Y.Hamuro, S.Raghuram, Y.Wang, T.P.Burris, and F.Rastinejad (2008).
Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA.
  Nature, 456, 350-356.
PDB codes: 3dzu 3dzy 3e00
17426125 M.Jakób, R.Kołodziejczyk, M.Orłowski, S.Krzywda, A.Kowalska, J.Dutko-Gwóźdź, T.Gwóźdź, M.Kochman, M.Jaskólski, and A.Ozyhar (2007).
Novel DNA-binding element within the C-terminal extension of the nuclear receptor DNA-binding domain.
  Nucleic Acids Res, 35, 2705-2718.
PDB code: 2han
16920361 C.Crane-Robinson, A.I.Dragan, and P.L.Privalov (2006).
The extended arms of DNA-binding domains: a tale of tails.
  Trends Biochem Sci, 31, 547-552.  
16931575 S.C.Roemer, D.C.Donham, L.Sherman, V.H.Pon, D.P.Edwards, and M.E.Churchill (2006).
Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.
  Mol Endocrinol, 20, 3042-3052.
PDB code: 2c7a
16849843 Y.Kanaho, D.Endo, and M.K.Park (2006).
Molecular characterization of thyroid hormone receptors from the leopard gecko, and their differential expression in the skin.
  Zoolog Sci, 23, 549-556.  
16085755 J.E.Donald, and E.I.Shakhnovich (2005).
Predicting specificity-determining residues in two large eukaryotic transcription factor families.
  Nucleic Acids Res, 33, 4455-4465.  
15572375 K.A.Temple, R.N.Cohen, S.R.Wondisford, C.Yu, D.Deplewski, and F.E.Wondisford (2005).
An intact DNA-binding domain is not required for peroxisome proliferator-activated receptor gamma (PPARgamma) binding and activation on some PPAR response elements.
  J Biol Chem, 280, 3529-3540.  
16130175 S.A.Khan, S.W.Park, M.Huq, and L.N.Wei (2005).
Protein kinase C-mediated phosphorylation of orphan nuclear receptor TR2: effects on receptor stability and activity.
  Proteomics, 5, 3885-3894.  
15611047 Y.Shostak, and K.R.Yamamoto (2005).
Overlapping but separable determinants of DNA binding and nuclear localization map to the C-terminal end of the Caenorhabditis elegans DAF-12 DNA binding domain.
  J Biol Chem, 280, 6554-6560.  
14739282 V.S.Melvin, C.Harrell, J.S.Adelman, W.L.Kraus, M.Churchill, and D.P.Edwards (2004).
The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB.
  J Biol Chem, 279, 14763-14771.  
12896978 C.Frank, M.M.Gonzalez, C.Oinonen, T.W.Dunlop, and C.Carlberg (2003).
Characterization of DNA complexes formed by the nuclear receptor constitutive androstane receptor.
  J Biol Chem, 278, 43299-43310.  
12533536 H.Fischer, S.M.Dias, M.A.Santos, A.C.Alves, N.Zanchin, A.F.Craievich, J.W.Apriletti, J.D.Baxter, P.Webb, F.A.Neves, R.C.Ribeiro, and I.Polikarpov (2003).
Low resolution structures of the retinoid X receptor DNA-binding and ligand-binding domains revealed by synchrotron X-ray solution scattering.
  J Biol Chem, 278, 16030-16038.  
14592980 S.Devarakonda, J.M.Harp, Y.Kim, A.Ozyhar, and F.Rastinejad (2003).
Structure of the heterodimeric ecdysone receptor DNA-binding complex.
  EMBO J, 22, 5827-5840.
PDB codes: 1r0n 1r0o
12377782 E.Raspè, G.Mautino, C.Duval, C.Fontaine, H.Duez, O.Barbier, D.Monte, J.Fruchart, J.C.Fruchart, and B.Staels (2002).
Transcriptional regulation of human Rev-erbalpha gene expression by the orphan nuclear receptor retinoic acid-related orphan receptor alpha.
  J Biol Chem, 277, 49275-49281.  
11773069 J.R.Schultz, M.A.Loven, V.M.Melvin, D.P.Edwards, and A.M.Nardulli (2002).
Differential modulation of DNA conformation by estrogen receptors alpha and beta.
  J Biol Chem, 277, 8702-8707.  
12210766 M.Quack, C.Frank, and C.Carlberg (2002).
Differential nuclear receptor signalling from DR4-type response elements.
  J Cell Biochem, 86, 601-612.  
11980721 P.L.Shaffer, and D.T.Gewirth (2002).
Structural basis of VDR-DNA interactions on direct repeat response elements.
  EMBO J, 21, 2242-2252.
PDB codes: 1kb2 1kb4 1kb6
12006575 V.S.Melvin, S.C.Roemer, M.E.Churchill, and D.P.Edwards (2002).
The C-terminal extension (CTE) of the nuclear hormone receptor DNA binding domain determines interactions and functional response to the HMGB-1/-2 co-regulatory proteins.
  J Biol Chem, 277, 25115-25124.  
11179889 F.Rastinejad (2001).
Retinoid X receptor and its partners in the nuclear receptor family.
  Curr Opin Struct Biol, 11, 33-38.  
11432742 I.Grad, A.Niedziela-Majka, M.Kochman, and A.Ozyhar (2001).
Analysis of Usp DNA binding domain targeting reveals critical determinants of the ecdysone receptor complex interaction with the response element.
  Eur J Biochem, 268, 3751-3758.  
11292843 N.V.Grishin (2001).
Treble clef finger--a functionally diverse zinc-binding structural motif.
  Nucleic Acids Res, 29, 1703-1714.  
11406412 S.Khorasanizadeh, and F.Rastinejad (2001).
Nuclear-receptor interactions on DNA-response elements.
  Trends Biochem Sci, 26, 384-390.  
11018291 C.Castagné, H.Terenzi, M.M.Zakin, and M.Delepierre (2000).
Solution structure of the orphan nuclear receptor rev-erb beta response element by 1H, 31P NMR and molecular simulation*.
  Biochimie, 82, 739-748.
PDB code: 1bn9
10698945 F.Rastinejad, T.Wagner, Q.Zhao, and S.Khorasanizadeh (2000).
Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.
  EMBO J, 19, 1045-1054.
PDB code: 1dsz
10845098 J.Zhang, and M.A.Lazar (2000).
The mechanism of action of thyroid hormones.
  Annu Rev Physiol, 62, 439-466.  
10753970 M.L.Hastings, H.A.Ingle, M.A.Lazar, and S.H.Munroe (2000).
Post-transcriptional regulation of thyroid hormone receptor expression by cis-acting sequences and a naturally occurring antisense RNA.
  J Biol Chem, 275, 11507-11513.  
10913286 P.J.van Tilborg, M.Czisch, F.A.Mulder, G.E.Folkers, A.M.Bonvin, M.Nair, R.Boelens, and R.Kaptein (2000).
Changes in dynamical behavior of the retinoid X receptor DNA-binding domain upon binding to a 14 base-pair DNA half site.
  Biochemistry, 39, 8747-8757.  
10470030 J.C.Dantonel, J.M.Wurtz, O.Poch, D.Moras, and L.Tora (1999).
The TBP-like factor: an alternative transcription factor in metazoa?
  Trends Biochem Sci, 24, 335-339.  
10220376 M.Kobayashi, S.Takezawa, K.Hara, R.T.Yu, Y.Umesono, K.Agata, M.Taniwaki, K.Yasuda, and K.Umesono (1999).
Identification of a photoreceptor cell-specific nuclear receptor.
  Proc Natl Acad Sci U S A, 96, 4814-4819.  
10438541 S.Chusacultanachai, K.A.Glenn, A.O.Rodriguez, E.K.Read, J.F.Gardner, B.S.Katzenellenbogen, and D.J.Shapiro (1999).
Analysis of estrogen response element binding by genetically selected steroid receptor DNA binding domain mutants exhibiting altered specificity and enhanced affinity.
  J Biol Chem, 274, 23591-23598.  
10375516 S.Khorasanizadeh, and F.Rastinejad (1999).
Transcription factors: the right combination for the DNA lock.
  Curr Biol, 9, R456-R458.  
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.