spacer
spacer

PDBsum entry 1dsz

Go to PDB code: 
protein dna_rna metals Protein-protein interface(s) links
Transcription/DNA PDB id
1dsz
Jmol
Contents
Protein chains
75 a.a. *
84 a.a. *
DNA/RNA
Metals
_ZN ×4
Waters ×338
* Residue conservation analysis
PDB id:
1dsz
Name: Transcription/DNA
Title: Structure of the rxr/rar DNA-binding domain heterodimer in complex with the retinoic acid response element dr1
Structure: DNA (5'- d( Cp Ap Gp Gp Tp Cp Ap Ap Ap Gp Gp Tp Cp Ap G)-3'). Chain: c. Engineered: yes. DNA (5'- d( Cp Tp Gp Ap Cp Cp Tp Tp Tp Gp Ap Cp Cp Tp G)-3'). Chain: d. Engineered: yes. Retinoic acid receptor alpha.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
1.70Å     R-factor:   0.198     R-free:   0.267
Authors: F.Rastinejad,T.Wagner,Q.Zhao,S.Khorasanizadeh
Key ref:
F.Rastinejad et al. (2000). Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1. EMBO J, 19, 1045-1054. PubMed id: 10698945 DOI: 10.1093/emboj/19.5.1045
Date:
10-Jan-00     Release date:   10-Jul-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10276  (RARA_HUMAN) -  Retinoic acid receptor alpha
Seq:
Struc:
462 a.a.
75 a.a.
Protein chain
Pfam   ArchSchema ?
P19793  (RXRA_HUMAN) -  Retinoic acid receptor RXR-alpha
Seq:
Struc:
462 a.a.
84 a.a.*
Key:    PfamA 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     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     DNA binding     6 terms  

 

 
DOI no: 10.1093/emboj/19.5.1045 EMBO J 19:1045-1054 (2000)
PubMed id: 10698945  
 
 
Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.
F.Rastinejad, T.Wagner, Q.Zhao, S.Khorasanizadeh.
 
  ABSTRACT  
 
The 9-cis retinoic acid receptor (retinoid X receptor, RXR) forms heterodimers with the all-trans retinoic acid receptor (RAR) and other nuclear receptors on DNA regulatory sites composed of tandem binding elements. We describe the 1.70 A resolution structure of the ternary complex of RXR and RAR DNA-binding regions in complex with the retinoic acid response element DR1. The receptors recognize identical half-sites through extensive base-specific contacts; however, RXR binds exclusively to the 3' site to form an asymmetric complex with the reverse polarity of other RXR heterodimers. The subunits associate in a strictly DNA-dependent manner using the T-box of RXR and the Zn-II region of RAR, both of which are reshaped in forming the complex. The protein-DNA contacts, the dimerization interface and the DNA curvature in the RXR-RAR complex are distinct from those of the RXR homodimer, which also binds DR1. Together, these structures illustrate how the nuclear receptor superfamily exploits conformational flexibility and locally induced structures to generate combinatorial transcription factors.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Stereo diagrams showing the contacts between the protein subunits. (A) The RXR–RAR interface involves the DNA minor groove and well ordered water molecules (red spheres). Dotted lines indicate hydrogen-bonding between atoms. The yellow spheres indicate the positions of the Zn-II atoms. Arg75 and Asn51 form complementary van der Waals interactions. (B) The corresponding region of the RXR–DBD homodimer interface on DR1 (Zhao et al., 2000). These and the following molecular display graphics were made using the program Ribbons (Carson and Bugg, 1986).
Figure 5.
Figure 5 DNA sequence recognition by RXR and RAR. (A) A view along the DNA-recognition helix ( 1) of RAR showing residues Tyr13, Arg26, Lys22, Glu19 and Arg27 and their direct and water-mediated base contacts. Hydrogen-bonds and water molecules are shown as dotted blue lines and red spheres, respectively. The DNA sequence is numbered as in Figure 1B. (B) The corresponding view of the RXR interface. (C) Summary of the protein–DNA contacts of RAR. Bridging water molecules are shown as black circles. The base pairs in blue form the consensus AGGTCA recognition element. The gray circles indicate the DNA phosphates. (D) Summary of RXR–DNA interactions. The base pairs in orange form the consensus element.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 1045-1054) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21414284 H.Urushitani, Y.Katsu, Y.Ohta, H.Shiraishi, T.Iguchi, and T.Horiguchi (2011).
Cloning and characterization of retinoid X receptor (RXR) isoforms in the rock shell, Thais clavigera.
  Aquat Toxicol, 103, 101-111.  
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.  
20097575 C.Bich, C.Bovet, N.Rochel, C.Peluso-Iltis, A.Panagiotidis, A.Nazabal, D.Moras, and R.Zenobi (2010).
Detection of nucleic acid-nuclear hormone receptor complexes with mass spectrometry.
  J Am Soc Mass Spectrom, 21, 635-645.  
20334529 R.Rohs, X.Jin, S.M.West, R.Joshi, B.Honig, and R.S.Mann (2010).
Origins of specificity in protein-DNA recognition.
  Annu Rev Biochem, 79, 233-269.  
  19471584 C.Rochette-Egly, and P.Germain (2009).
Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
  Nucl Recept Signal, 7, e005.  
19341714 H.L.Zhao, N.Ueki, K.Marcelain, and M.J.Hayman (2009).
The Ski protein can inhibit ligand induced RARalpha and HDAC3 degradation in the retinoic acid signaling pathway.
  Biochem Biophys Res Commun, 383, 119-124.  
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.  
20052392 L.S.Chan, and R.A.Wells (2009).
Cross-Talk between PPARs and the Partners of RXR: A Molecular Perspective.
  PPAR Res, 2009, 925309.  
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.  
19416983 Y.H.Han, H.Zhou, J.H.Kim, T.D.Yan, K.H.Lee, H.Wu, F.Lin, N.Lu, J.Liu, J.Z.Zeng, and X.K.Zhang (2009).
A Unique Cytoplasmic Localization of Retinoic Acid Receptor-{gamma} and Its Regulations.
  J Biol Chem, 284, 18503-18514.  
19472184 Z.Chai, L.Yang, B.Yu, Q.He, W.I.Li, R.Zhou, T.Zhang, X.Zheng, and J.Xie (2009).
p38 mitogen-activated protein kinase-dependent regulation of SRC-3 and involvement in retinoic acid receptor alpha signaling in embryonic cortical neurons.
  IUBMB Life, 61, 670-678.  
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.  
18179707 S.D.DeMeo, R.M.Lombel, M.Cronin, E.L.Smith, D.R.Snowflack, K.Reinert, S.Clever, and B.Wightman (2008).
Specificity of DNA-binding by the FAX-1 and NHR-67 nuclear receptors of Caenorhabditis elegans is partially mediated via a subclass-specific P-box residue.
  BMC Mol Biol, 9, 2.  
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
17320364 M.M.McGrane (2007).
Vitamin A regulation of gene expression: molecular mechanism of a prototype gene.
  J Nutr Biochem, 18, 497-508.  
16894153 D.C.Wan, Y.Y.Shi, R.P.Nacamuli, N.Quarto, K.M.Lyons, and M.T.Longaker (2006).
Osteogenic differentiation of mouse adipose-derived adult stromal cells requires retinoic acid and bone morphogenetic protein receptor type IB signaling.
  Proc Natl Acad Sci U S A, 103, 12335-12340.  
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
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.  
16175536 S.C.Perera, S.Zheng, Q.L.Feng, P.J.Krell, A.Retnakaran, and S.R.Palli (2005).
Heterodimerization of ecdysone receptor and ultraspiracle on symmetric and asymmetric response elements.
  Arch Insect Biochem Physiol, 60, 55-70.  
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.  
15340076 A.Szanto, S.Benko, I.Szatmari, B.L.Balint, I.Furtos, R.Rühl, S.Molnar, L.Csiba, R.Garuti, S.Calandra, H.Larsson, U.Diczfalusy, and L.Nagy (2004).
Transcriptional regulation of human CYP27 integrates retinoid, peroxisome proliferator-activated receptor, and liver X receptor signaling in macrophages.
  Mol Cell Biol, 24, 8154-8166.  
15037741 P.L.Shaffer, A.Jivan, D.E.Dollins, F.Claessens, and D.T.Gewirth (2004).
Structural basis of androgen receptor binding to selective androgen response elements.
  Proc Natl Acad Sci U S A, 101, 4758-4763.
PDB code: 1r4i
15509776 X.Cao, W.Liu, F.Lin, H.Li, S.K.Kolluri, B.Lin, Y.H.Han, M.I.Dawson, and X.K.Zhang (2004).
Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting.
  Mol Cell Biol, 24, 9705-9725.  
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
14560013 V.Vivat-Hannah, W.Bourguet, M.Gottardis, and H.Gronemeyer (2003).
Separation of retinoid X receptor homo- and heterodimerization functions.
  Mol Cell Biol, 23, 7678-7688.  
11812777 E.Kanaya, N.Nakajima, and K.Okada (2002).
Non-sequence-specific DNA binding by the FILAMENTOUS FLOWER protein from Arabidopsis thaliana is reduced by EDTA.
  J Biol Chem, 277, 11957-11964.  
11970949 F.E.Chen-Park, D.B.Huang, B.Noro, D.Thanos, and G.Ghosh (2002).
The kappa B DNA sequence from the HIV long terminal repeat functions as an allosteric regulator of HIV transcription.
  J Biol Chem, 277, 24701-24708.
PDB code: 1lei
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.  
11719067 G.Jones, M.Wozniak, Y.Chu, S.Dhar, and D.Jones (2001).
Juvenile hormone III-dependent conformational changes of the nuclear receptor ultraspiracle.
  Insect Biochem Mol Biol, 32, 33-49.  
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.  
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.