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protein dna_rna metals Protein-protein interface(s) links
Transcription/DNA PDB id
1hcq
Jmol
Contents
Protein chains
74 a.a. *
DNA/RNA
Metals
_ZN ×8
Waters ×158
* Residue conservation analysis
PDB id:
1hcq
Name: Transcription/DNA
Title: The crystal structure of the estrogen receptor DNA-binding domain bound to dna: how receptors discriminate between their response elements
Structure: DNA (5'- d( Cp Cp Ap Gp Gp Tp Cp Ap Cp Ap Gp Tp Gp Ap Cp Cp T p G)- 3'). Chain: c, g. Engineered: yes. DNA (5'- d( Cp Cp Ap Gp Gp Tp Cp Ap Cp Tp Gp Tp Gp Ap Cp Cp T p G)- 3'). Chain: d, h.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.204    
Authors: J.W.R.Schwabe,L.Chapman,J.T.Finch,D.Rhodes
Key ref: J.W.Schwabe et al. (1993). The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell, 75, 567-578. PubMed id: 8221895 DOI: 10.1016/0092-8674(93)90390-C
Date:
04-Jan-95     Release date:   23-Nov-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P03372  (ESR1_HUMAN) -  Estrogen receptor
Seq:
Struc:
 
Seq:
Struc:
595 a.a.
74 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     5 terms  

 

 
DOI no: 10.1016/0092-8674(93)90390-C Cell 75:567-578 (1993)
PubMed id: 8221895  
 
 
The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements.
J.W.Schwabe, L.Chapman, J.T.Finch, D.Rhodes.
 
  ABSTRACT  
 
The nuclear hormone receptors are a superfamily of ligand-activated DNA-binding transcription factors. We have determined the crystal structure (at 2.4 A) of the fully specific complex between the DNA-binding domain from the estrogen receptor and DNA. The protein binds as a symmetrical dimer to its palindromic binding site consisting of two 6 bp consensus half sites with three intervening base pairs. This structure reveals how the protein recognizes its own half site sequence rather than that of the related glucocorticoid receptor, which differs by only two base pairs. Since all nuclear hormone receptors recognize one or the other of these two consensus half site sequences, this recognition mechanism applies generally to the whole receptor family.
 

Literature references that cite this PDB file's key reference

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Phosphorylation of thyroid hormone receptors by protein kinase A regulates DNA recognition by specific inhibition of receptor monomer binding.
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  9821279 D.E.Mossakowska (1998).
Expression of nuclear hormone receptors in Escherichia coli.
  Curr Opin Biotechnol, 9, 502-505.  
9600906 D.M.Tanenbaum, Y.Wang, S.P.Williams, and P.B.Sigler (1998).
Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains.
  Proc Natl Acad Sci U S A, 95, 5998-6003.
PDB code: 1a52
9708984 H.Terenzi, P.M.Alzari, and M.M.Zakin (1998).
Structural features involved in the formation of a complex between the monomeric or the dimeric form of the rev-erb beta DNA-binding domain and its DNA reactive sites.
  Biochemistry, 37, 11488-11495.  
9597142 J.D.Klemm, S.L.Schreiber, and G.R.Crabtree (1998).
Dimerization as a regulatory mechanism in signal transduction.
  Annu Rev Immunol, 16, 569-592.  
  9528764 J.R.Wood, G.L.Greene, and A.M.Nardulli (1998).
Estrogen response elements function as allosteric modulators of estrogen receptor conformation.
  Mol Cell Biol, 18, 1927-1934.  
9792632 M.D.Driscoll, G.Sathya, M.Muyan, C.M.Klinge, R.Hilf, and R.A.Bambara (1998).
Sequence requirements for estrogen receptor binding to estrogen response elements.
  J Biol Chem, 273, 29321-29330.  
9580693 M.Vögtli, C.Elke, M.O.Imhof, and M.Lezzi (1998).
High level transactivation by the ecdysone receptor complex at the core recognition motif.
  Nucleic Acids Res, 26, 2407-2414.  
9660968 Q.Zhao, S.Khorasanizadeh, Y.Miyoshi, M.A.Lazar, and F.Rastinejad (1998).
Structural elements of an orphan nuclear receptor-DNA complex.
  Mol Cell, 1, 849-861.
PDB code: 1a6y
9665167 R.B.Turner, D.L.Smith, M.E.Zawrotny, M.F.Summers, M.C.Posewitz, and D.R.Winge (1998).
Solution structure of a zinc domain conserved in yeast copper-regulated transcription factors.
  Nat Struct Biol, 5, 551-555.
PDB code: 1co4
  9671457 V.Boonyaratanakornkit, V.Melvin, P.Prendergast, M.Altmann, L.Ronfani, M.E.Bianchi, L.Taraseviciene, S.K.Nordeen, E.A.Allegretto, and D.P.Edwards (1998).
High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells.
  Mol Cell Biol, 18, 4471-4487.  
  9023209 A.L.Donner, P.A.Carlson, and G.B.Koudelka (1997).
Dimerization specificity of P22 and 434 repressors is determined by multiple polypeptide segments.
  J Bacteriol, 179, 1253-1261.  
9395481 C.M.Klinge, B.F.Silver, M.D.Driscoll, G.Sathya, R.A.Bambara, and R.Hilf (1997).
Chicken ovalbumin upstream promoter-transcription factor interacts with estrogen receptor, binds to estrogen response elements and half-sites, and inhibits estrogen-induced gene expression.
  J Biol Chem, 272, 31465-31474.  
9049312 D.Curtis, D.K.Treiber, F.Tao, P.D.Zamore, J.R.Williamson, and R.Lehmann (1997).
A CCHC metal-binding domain in Nanos is essential for translational regulation.
  EMBO J, 16, 834-843.  
9251777 D.Kosztin, T.C.Bishop, and K.Schulten (1997).
Binding of the estrogen receptor to DNA. The role of waters.
  Biophys J, 73, 557-570.  
9218433 D.S.Sem, D.R.Casimiro, S.A.Kliewer, J.Provencal, R.M.Evans, and P.E.Wright (1997).
NMR spectroscopic studies of the DNA-binding domain of the monomer-binding nuclear orphan receptor, human estrogen related receptor-2. The carboxyl-terminal extension to the zinc-finger region is unstructured in the free form of the protein.
  J Biol Chem, 272, 18038-18043.  
  9345851 G.Capranico, M.Binaschi, M.E.Borgnetto, F.Zunino, and M.Palumbo (1997).
A protein-mediated mechanism for the DNA sequence-specific action of topoisomerase II poisons.
  Trends Pharmacol Sci, 18, 323-329.  
9342356 G.E.Carney, A.A.Wade, R.Sapra, E.S.Goldstein, and M.Bender (1997).
DHR3, an ecdysone-inducible early-late gene encoding a Drosophila nuclear receptor, is required for embryogenesis.
  Proc Natl Acad Sci U S A, 94, 12024-12029.  
8995424 G.Jiang, and F.M.Sladek (1997).
The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative, specific binding to DNA and heterodimerization with the retinoid X receptor alpha.
  J Biol Chem, 272, 1218-1225.  
  9343418 G.Jiang, U.Lee, and F.M.Sladek (1997).
Proposed mechanism for the stabilization of nuclear receptor DNA binding via protein dimerization.
  Mol Cell Biol, 17, 6546-6554.  
9241421 G.Patikoglou, and S.K.Burley (1997).
Eukaryotic transcription factor-DNA complexes.
  Annu Rev Biophys Biomol Struct, 26, 289-325.  
9287161 H.Berglund, M.Wolf-Watz, T.Lundbäck, S.van den Berg, and T.Härd (1997).
Structure and dynamics of the glucocorticoid receptor DNA-binding domain: comparison of wild type and a mutant with altered specificity.
  Biochemistry, 36, 11188-11197.  
  9154816 J.Kim, G.de Haan, A.M.Nardulli, and D.J.Shapiro (1997).
Prebending the estrogen response element destabilizes binding of the estrogen receptor DNA binding domain.
  Mol Cell Biol, 17, 3173-3180.  
9032063 J.W.Schwabe (1997).
The role of water in protein-DNA interactions.
  Curr Opin Struct Biol, 7, 126-134.  
  9570132 K.Grandien, A.Berkenstam, and J.A.Gustafsson (1997).
The estrogen receptor gene: promoter organization and expression.
  Int J Biochem Cell Biol, 29, 1343-1369.  
9346945 M.A.Kuntz, and D.J.Shapiro (1997).
Dimerizing the estrogen receptor DNA binding domain enhances binding to estrogen response elements.
  J Biol Chem, 272, 27949-27956.  
9100018 M.K.Bhat, P.McPhie, and S.Cheng (1997).
Critical role of glutamine 252 in the hormone-dependent transcriptional activity of the thyroid hormone beta1 nuclear receptor.
  Biochemistry, 36, 4233-4239.  
9374531 M.S.Ozers, J.J.Hill, K.Ervin, J.R.Wood, A.M.Nardulli, C.A.Royer, and J.Gorski (1997).
Equilibrium binding of estrogen receptor with DNA using fluorescence anisotropy.
  J Biol Chem, 272, 30405-30411.  
9033395 P.Doesburg, C.W.Kuil, C.A.Berrevoets, K.Steketee, P.W.Faber, E.Mulder, A.O.Brinkmann, and J.Trapman (1997).
Functional in vivo interaction between the amino-terminal, transactivation domain and the ligand binding domain of the androgen receptor.
  Biochemistry, 36, 1052-1064.  
9325313 P.Pace, J.Taylor, S.Suntharalingam, R.C.Coombes, and S.Ali (1997).
Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha.
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9782776 R.E.Dickerson, and T.K.Chiu (1997).
Helix bending as a factor in protein/DNA recognition.
  Biopolymers, 44, 361-403.  
9242648 S.M.Cowley, S.Hoare, S.Mosselman, and M.G.Parker (1997).
Estrogen receptors alpha and beta form heterodimers on DNA.
  J Biol Chem, 272, 19858-19862.  
9129808 T.C.Bishop, D.Kosztin, and K.Schulten (1997).
How hormone receptor-DNA binding affects nucleosomal DNA: the role of symmetry.
  Biophys J, 72, 2056-2067.  
  9168467 Y.Tang, C.Ramakrishnan, J.Thomas, and D.B.DeFranco (1997).
A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and transrepression defects of a glucocorticoid receptor zinc finger mutant.
  Mol Biol Cell, 8, 795-809.  
  8622645 B.D.Lemon, and L.P.Freedman (1996).
Selective effects of ligands on vitamin D3 receptor- and retinoid X receptor-mediated gene activation in vivo.
  Mol Cell Biol, 16, 1006-1016.  
8702636 C.C.Nelson, S.C.Hendy, J.S.Faris, and P.J.Romaniuk (1996).
Retinoid X receptor alters the determination of DNA binding specificity by the P-box amino acids of the thyroid hormone receptor.
  J Biol Chem, 271, 19464-19474.  
  9000009 D.A.Erlanson, M.Chytil, and G.L.Verdine (1996).
The leucine zipper domain controls the orientation of AP-1 in the NFAT.AP-1.DNA complex.
  Chem Biol, 3, 981-991.  
8617792 D.Conte, S.Narindrasorasak, and B.Sarkar (1996).
In vivo and in vitro iron-replaced zinc finger generates free radicals and causes DNA damage.
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8761938 D.G.Mottershead, P.Polly, R.J.Lyons, R.L.Sutherland, and C.K.Watts (1996).
High activity, soluble, bacterially expressed human vitamin D receptor and its ligand binding domain.
  J Cell Biochem, 61, 325-337.  
8734007 J.H.Pinter, C.Deep, and O.K.Park-Sarge (1996).
Progesterone receptors: expression and regulation in the mammalian ovary.
  Clin Obstet Gynecol, 39, 424-435.  
8723335 J.W.Schwabe (1996).
Transcriptional control: how nuclear receptors get turned on.
  Curr Biol, 6, 372-374.  
  9004761 L.S.Yasui, A.Hughes, and E.R.DeSombre (1996).
DNA damage induction by 125I-estrogen.
  Acta Oncol, 35, 841-847.  
8994885 M.A.Navia (1996).
Protein-drug complexes important for immunoregulation and organ transplantation.
  Curr Opin Struct Biol, 6, 838-847.  
8651621 M.Beato, M.Truss, and S.Chávez (1996).
Control of transcription by steroid hormones.
  Ann N Y Acad Sci, 784, 93.  
  8947052 M.P.Kladde, M.Xu, and R.T.Simpson (1996).
Direct study of DNA-protein interactions in repressed and active chromatin in living cells.
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17029807 T.Härd, and T.Lundbäck (1996).
Thermodynamics of sequence-specific protein-DNA interactions.
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8643475 T.Lundbäck, and T.Härd (1996).
Sequence-specific DNA-binding dominated by dehydration.
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  7891721 A.H.Swirnoff, and J.Milbrandt (1995).
DNA-binding specificity of NGFI-A and related zinc finger transcription factors.
  Mol Cell Biol, 15, 2275-2287.  
7625690 A.Klug (1995).
Gene regulatory proteins and their interaction with DNA.
  Ann N Y Acad Sci, 758, 143-160.  
  8575189 A.M.Gronenborn, and G.M.Clore (1995).
Structures of protein complexes by multidimensional heteronuclear magnetic resonance spectroscopy.
  Crit Rev Biochem Mol Biol, 30, 351-385.  
7625727 B.M.Forman, and R.M.Evans (1995).
Nuclear hormone receptors activate direct, inverted, and everted repeats.
  Ann N Y Acad Sci, 761, 29-37.  
7622518 C.C.Nelson, S.C.Hendy, and P.J.Romaniuk (1995).
Relationship between P-box amino acid sequence and DNA binding specificity of the thyroid hormone receptor. The effects of half-site sequence in everted repeats.
  J Biol Chem, 270, 16981-16987.  
7622519 C.C.Nelson, S.C.Hendy, and P.J.Romaniuk (1995).
Relationship between P-box amino acid sequence and DNA binding specificity of the thyroid hormone receptor. The effects of sequences flanking half-sites in thyroid hormone response elements.
  J Biol Chem, 270, 16988-16994.  
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New Insights into the Structure and Function of the Thyroid Hormone Receptor.
  J Biomed Sci, 2, 77-89.  
8521508 D.J.Mangelsdorf, and R.M.Evans (1995).
The RXR heterodimers and orphan receptors.
  Cell, 83, 841-850.  
7664096 D.T.Gewirth, and P.B.Sigler (1995).
The basis for half-site specificity explored through a non-cognate steroid receptor-DNA complex.
  Nat Struct Biol, 2, 386-394.
PDB code: 1lat
  8593870 G.M.Stancel, H.L.Boettger-Tong, C.Chiappetta, S.M.Hyder, J.L.Kirkland, L.Murthy, and D.S.Loose-Mitchell (1995).
Toxicity of endogenous and environmental estrogens: what is the role of elemental interactions?
  Environ Health Perspect, 103, 29-33.  
7601148 H.Baumann, and T.Härd (1995).
Structural characterization of a short peptide fragment that mediates estrogen-receptor dimerization.
  Eur J Biochem, 230, 879-885.  
7635163 H.H.Thole, I.Maschler, and P.W.Jungblut (1995).
Surface mapping of the ligand-filled C-terminal half of the porcine estradiol receptor by restricted proteolysis.
  Eur J Biochem, 231, 510-516.  
  7651396 H.P.Harding, and M.A.Lazar (1995).
The monomer-binding orphan receptor Rev-Erb represses transcription as a dimer on a novel direct repeat.
  Mol Cell Biol, 15, 4791-4802.  
7559612 J.A.Lupisella, J.E.Driscoll, W.J.Metzler, and P.R.Reczek (1995).
The ligand binding domain of the human retinoic acid receptor gamma is predominantly alpha-helical with a Trp residue in the ligand binding site.
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7501014 J.P.Renaud, N.Rochel, M.Ruff, V.Vivat, P.Chambon, H.Gronemeyer, and D.Moras (1995).
Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid.
  Nature, 378, 681-689.
PDB code: 2lbd
  7735836 J.W.Schwabe, L.Chapman, and D.Rhodes (1995).
The oestrogen receptor recognizes an imperfectly palindromic response element through an alternative side-chain conformation.
  Structure, 3, 201-213.  
7716169 J.Zilliacus, A.P.Wright, J.Carlstedt-Duke, L.Nilsson, and J.A.Gustafsson (1995).
Modulation of DNA-binding specificity within the nuclear receptor family by substitutions at a single amino acid position.
  Proteins, 21, 57-67.  
  7823947 L.D.McBroom, G.Flock, and V.Giguère (1995).
The nonconserved hinge region and distinct amino-terminal domains of the ROR alpha orphan nuclear receptor isoforms are required for proper DNA bending and ROR alpha-DNA interactions.
  Mol Cell Biol, 15, 796-808.  
7696496 M.A.Eriksson, T.Härd, and L.Nilsson (1995).
Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain in complex with DNA and free in solution.
  Biophys J, 68, 402-426.  
8579895 M.R.Haussler, P.W.Jurutka, J.C.Hsieh, P.D.Thompson, S.H.Selznick, C.A.Haussler, and G.K.Whitfield (1995).
New understanding of the molecular mechanism of receptor-mediated genomic actions of the vitamin D hormone.
  Bone, 17, 33S-38S.  
8749848 M.Suzuki, and M.Gerstein (1995).
Binding geometry of alpha-helices that recognize DNA.
  Proteins, 23, 525-535.  
7664086 N.D.Arbuckle, and B.Luisi (1995).
A recipe for specificity.
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7501015 R.L.Wagner, J.W.Apriletti, M.E.McGrath, B.L.West, J.D.Baxter, and R.J.Fletterick (1995).
A structural role for hormone in the thyroid hormone receptor.
  Nature, 378, 690-697.  
  7565738 S.Kato, H.Sasaki, M.Suzawa, S.Masushige, L.Tora, P.Chambon, and H.Gronemeyer (1995).
Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors.
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7589783 S.M.Hyder, G.L.Shipley, and G.M.Stancel (1995).
Estrogen action in target cells: selective requirements for activation of different hormone response elements.
  Mol Cell Endocrinol, 112, 35-43.  
  7739535 V.Giguère, L.D.McBroom, and G.Flock (1995).
Determinants of target gene specificity for ROR alpha 1: monomeric DNA binding by an orphan nuclear receptor.
  Mol Cell Biol, 15, 2517-2526.  
7828346 A.R.Rut, M.Hewison, K.Kristjansson, B.Luisi, M.R.Hughes, and J.L.O'Riordan (1994).
Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA-binding domain crystal structures.
  Clin Endocrinol (Oxf), 41, 581-590.  
  8137826 C.Zechel, X.Q.Shen, J.Y.Chen, Z.P.Chen, P.Chambon, and H.Gronemeyer (1994).
The dimerization interfaces formed between the DNA binding domains of RXR, RAR and TR determine the binding specificity and polarity of the full-length receptors to direct repeats.
  EMBO J, 13, 1425-1433.  
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Dimerization interfaces formed between the DNA binding domains determine the cooperative binding of RXR/RAR and RXR/TR heterodimers to DR5 and DR4 elements.
  EMBO J, 13, 1414-1424.  
  8168495 F.Bouillaud, I.Arechaga, P.X.Petit, S.Raimbault, C.Levi-Meyrueis, L.Casteilla, M.Laurent, E.Rial, and D.Ricquier (1994).
A sequence related to a DNA recognition element is essential for the inhibition by nucleotides of proton transport through the mitochondrial uncoupling protein.
  EMBO J, 13, 1990-1997.  
  8019409 G.M.Clore, and A.M.Gronenborn (1994).
Young Investigator Award Lecture. Structures of larger proteins, protein-ligand and protein-DNA complexes by multidimensional heteronuclear NMR.
  Protein Sci, 3, 372-390.  
7664042 J.W.Schwabe, and A.Klug (1994).
Zinc mining for protein domains.
  Nat Struct Biol, 1, 345-349.  
7925381 M.S.Lee, D.S.Sem, S.A.Kliewer, J.Provencal, R.M.Evans, and P.E.Wright (1994).
NMR assignments and secondary structure of the retinoid X receptor alpha DNA-binding domain. Evidence for the novel C-terminal helix.
  Eur J Biochem, 224, 639-650.  
7809040 M.Suzuki, and N.Yagi (1994).
DNA recognition code of transcription factors in the helix-turn-helix, probe helix, hormone receptor, and zinc finger families.
  Proc Natl Acad Sci U S A, 91, 12357-12361.  
  8087558 M.Suzuki (1994).
A framework for the DNA-protein recognition code of the probe helix in transcription factors: the chemical and stereochemical rules.
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8001144 P.Sengupta, H.A.Colbert, and C.I.Bargmann (1994).
The C. elegans gene odr-7 encodes an olfactory-specific member of the nuclear receptor superfamily.
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  16100953 J.W.Schwabe, L.Chapman, J.T.Finch, D.Rhodes, and D.Neuhaus (1993).
DNA recognition by the oestrogen receptor: from solution to the crystal.
  Structure, 1, 187-204.
PDB code: 1hcp
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