Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Scarab Genomics

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 13 July 1990:
Vol. 249. no. 4965, pp. 157 - 160
DOI: 10.1126/science.2115209

Articles

Science, Vol 249, Issue 4965, 157-160
Copyright © 1990 by American Association for the Advancement of Science


articles

Solution structure of the glucocorticoid receptor DNA-binding domain

T Hard, E Kellenbach, R Boelens, BA Maler, K Dahlman, LP Freedman, J Carlstedt-Duke, KR Yamamoto, JA Gustafsson, and R Kaptein

Department of Chemistry, University of Utrecht, The Netherlands.

The three-dimensional structure of the DNA-binding domain (DBD) of the glucocorticoid receptor has been determined by nuclear magnetic resonance spectroscopy and distance geometry. The structure of a 71-residue protein fragment containing two "zinc finger" domains is based on a large set of proton-proton distances derived from nuclear Overhauser enhancement spectra, hydrogen bonds in previously identified secondary structure elements, and coordination of two zinc atoms by conserved cysteine residues. The DBD is found to consist of a globular body from which the finger regions extend. A model of the dimeric complex between the DBD and the glucocorticoid response element is proposed. The model is consistent with previous results indicating that specific amino acid residues of the DBD are involved in protein-DNA and protein-protein interactions.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Nuclear Receptors and Female Reproduction: A Tale of 3 Scientists, Jensen, Gustafsson, and O'Malley.
G. Chaudhuri (2008)
Reproductive Sciences 15, 110-120
   Abstract »    PDF »
A Membrane-proximal Tetracysteine Motif Contributes to Assembly of CD3{delta}{epsilon} and CD3{gamma}{epsilon} Dimers with the T Cell Receptor.
C. Xu, M. E. Call, and K. W. Wucherpfennig (2006)
J. Biol. Chem. 281, 36977-36984
   Abstract »    Full Text »    PDF »
Progesterone Receptors (PR)-B and -A Regulate Transcription by Different Mechanisms: AF-3 Exerts Regulatory Control over Coactivator Binding to PR-B.
L. Tung, H. Abdel-Hafiz, T. Shen, D. M. E. Harvell, L. K. Nitao, J. K. Richer, C. A. Sartorius, G. S. Takimoto, and K. B. Horwitz (2006)
Mol. Endocrinol. 20, 2656-2670
   Abstract »    Full Text »    PDF »
Evolution of glucocorticoid receptors with different glucocorticoid sensitivity..
E. H Stolte, B M L. V. van Kemenade, H. F J Savelkoul, and G. Flik (2006)
J. Endocrinol. 190, 17-28
   Abstract »    Full Text »    PDF »
Activation Function 1 of Glucocorticoid Receptor Binds TATA-Binding Protein in Vitro and in Vivo.
A. J. Copik, M. S. Webb, A. L. Miller, Y. Wang, R. Kumar, and E. B. Thompson (2006)
Mol. Endocrinol. 20, 1218-1230
   Abstract »    Full Text »    PDF »
Steroids and the Scientist.
J.-A. Gustafsson (2005)
Mol. Endocrinol. 19, 1412-1417
   Abstract »    Full Text »    PDF »
Protein-Protein Interactions and Transcriptional Antagonism between the Subfamily of NGFI-B/Nur77 Orphan Nuclear Receptors and Glucocorticoid Receptor.
C. Martens, S. Bilodeau, M. Maira, Y. Gauthier, and J. Drouin (2005)
Mol. Endocrinol. 19, 885-897
   Abstract »    Full Text »    PDF »
Glucocorticoid Receptor Ligand Binding Domain Is Sufficient for the Modulation of Glucocorticoid Induction Properties by Homologous Receptors, Coactivator Transcription Intermediary Factor 2, and Ubc9.
S. Cho, B. L. Kagan, J. A. Blackford Jr., D. Szapary, and S. S. Simons Jr. (2005)
Mol. Endocrinol. 19, 290-311
   Abstract »    Full Text »    PDF »
A Single Amino Acid Change in the First Zinc Finger of the DNA Binding Domain of the Glucocorticoid Receptor Regulates Differential Promoter Selectivity.
B. M. Necela and J. A. Cidlowski (2004)
J. Biol. Chem. 279, 39279-39288
   Abstract »    Full Text »    PDF »
Tip110, the Human Immunodeficiency Virus Type 1 (HIV-1) Tat-interacting Protein of 110 kDa as a Negative Regulator of Androgen Receptor (AR) Transcriptional Activation.
Y. Liu, B. O. Kim, C. Kao, C. Jung, J. T. Dalton, and J. J. He (2004)
J. Biol. Chem. 279, 21766-21773
   Abstract »    Full Text »    PDF »
Inaugural Article: Biography of Jan-Ake Gustafsson.
C. Brownlee (2004)
PNAS 101, 3737-3738
   Full Text »    PDF »
The Divergent Orphan Nuclear Receptor ODR-7 Regulates Olfactory Neuron Gene Expression via Multiple Mechanisms in Caenorhabditis elegans.
M. E. Colosimo, S. Tran, and P. Sengupta (2003)
Genetics 165, 1779-1791
   Abstract »    Full Text »    PDF »
The Three-dimensional Structures of Antagonistic and Agonistic Forms of the Glucocorticoid Receptor Ligand-binding Domain: RU-486 INDUCES A TRANSCONFORMATION THAT LEADS TO ACTIVE ANTAGONISM.
B. Kauppi, C. Jakob, M. Farnegardh, J. Yang, H. Ahola, M. Alarcon, K. Calles, O. Engstrom, J. Harlan, S. Muchmore, et al. (2003)
J. Biol. Chem. 278, 22748-22754
   Abstract »    Full Text »    PDF »
The nuclear receptor superfamily.
M. Robinson-Rechavi, H. E. Garcia, and V. Laudet (2003)
J. Cell Sci. 116, 585-586
   Full Text »    PDF »
Molecular Biology of the Androgen Receptor.
E. P. Gelmann (2002)
J. Clin. Oncol. 20, 3001-3015
   Abstract »    Full Text »    PDF »
Tip60 Is a Co-activator Specific for Class I Nuclear Hormone Receptors.
L. Gaughan, M. E. Brady, S. Cook, D. E. Neal, and C. N. Robson (2001)
J. Biol. Chem. 276, 46841-46848
   Abstract »    Full Text »    PDF »
Suppression of Granulocyte-Macrophage Colony-Stimulating Factor Expression by Glucocorticoids Involves Inhibition of Enhancer Function by the Glucocorticoid Receptor Binding to Composite NF-AT/Activator Protein-1 Elements.
P. J. Smith, D. J. Cousins, Y.-K. Jee, D. Z. Staynov, T. H. Lee, and P. Lavender (2001)
J. Immunol. 167, 2502-2510
   Abstract »    Full Text »    PDF »
Nuclear Hormone Receptors and Gene Expression.
A. Aranda and A. Pascual (2001)
Physiol Rev 81, 1269-1304
   Abstract »    Full Text »    PDF »
Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers.
L. Zhu, J. Wilken, N. B. Phillips, U. Narendra, G. Chan, S. M. Stratton, S. B. Kent, and M. A. Weiss (2000)
Genes & Dev. 14, 1750-1764
   Abstract »    Full Text »
Differences in DNA Binding Characteristics of the Androgen and Glucocorticoid Receptors Can Determine Hormone-specific Responses.
E. Schoenmakers, G. Verrijdt, B. Peeters, G. Verhoeven, W. Rombauts, and F. Claessens (2000)
J. Biol. Chem. 275, 12290-12297
   Abstract »    Full Text »    PDF »
A C619Y Mutation in the Human Androgen Receptor Causes Inactivation and Mislocalization of the Receptor with Concomitant Sequestration of SRC-1 (Steroid Receptor Coactivator 1).
L. V. Nazareth, D. L. Stenoien, W. E. Bingman III, A. J. James, C. Wu, Y. Zhang, D. P. Edwards, M. Mancini, M. Marcelli, D. J. Lamb, et al. (1999)
Mol. Endocrinol. 13, 2065-2075
   Abstract »    Full Text »
Glycine Insertion in the Hinge Region of Lactose Repressor Protein Alters DNA Binding.
C. M. Falcon and K. S. Matthews (1999)
J. Biol. Chem. 274, 30849-30857
   Abstract »    Full Text »    PDF »
Composite Glucocorticoid Regulation at a Functionally Defined Negative Glucocorticoid Response Element of the Human Corticotropin-Releasing Hormone Gene.
S. P. Malkoski and R. I. Dorin (1999)
Mol. Endocrinol. 13, 1629-1644
   Abstract »    Full Text »
Function of Steroidogenic Factor 1 Domains in Nuclear Localization, Transactivation, and Interaction with Transcription Factor TFIIB and c-Jun.
L.-A. Li, E. F-L. Chiang, J.-C. Chen, N.-C. Hsu, Y.-J. Chen, and B.-c. Chung (1999)
Mol. Endocrinol. 13, 1588-1598
   Abstract »    Full Text »
Interdomain Signaling in a Two-domain Fragment of the Human Glucocorticoid Receptor.
R. Kumar, I. V. Baskakov, G. Srinivasan, D. W. Bolen, J. C. Lee, and E. B. Thompson (1999)
J. Biol. Chem. 274, 24737-24741
   Abstract »    Full Text »    PDF »
Transcription Activating and Repressing Functions of the Androgen Receptor Are Differentially Influenced by Mutations in the Deoxyribonucleic Acid-Binding Domain.
P. Aarnisalo, H. Santti, H. Poukka, J. J. Palvimo, and O. A. Jänne (1999)
Endocrinology 140, 3097-3105
   Abstract »    Full Text »
Trimethylamine N-Oxide-induced Cooperative Folding of an Intrinsically Unfolded Transcription-activating Fragment of Human Glucocorticoid Receptor.
I. V. Baskakov, R. Kumar, G. Srinivasan, Y.-s. Ji, D. W. Bolen, and E. B. Thompson (1999)
J. Biol. Chem. 274, 10693-10696
   Abstract »    Full Text »    PDF »
The Vitamin D Receptor and the Syndrome of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets.
P. J. Malloy, J. W. Pike, and D. Feldman (1999)
Endocr. Rev. 20, 156-188
   Abstract »    Full Text »
Expression of the Human Endogenous Retrovirus HTDV/HERV-K Is Enhanced by Cellular Transcription Factor YY1.
M. Knössl, R. Löwer, and J. Löwer (1999)
J. Virol. 73, 1254-1261
   Abstract »    Full Text »
Estrogen Response Elements Function as Allosteric Modulators of Estrogen Receptor Conformation.
J. R. Wood, G. L. Greene, and A. M. Nardulli (1998)
Mol. Cell. Biol. 18, 1927-1934
   Abstract »    Full Text »
TLS (Translocated-in-Liposarcoma) Is a High-Affinity Interactor for Steroid, Thyroid Hormone, and Retinoid Receptors.
C. A. Powers, M. Mathur, B. M. Raaka, D. Ron, and H. H. Samuels (1998)
Mol. Endocrinol. 12, 4-18
   Abstract »    Full Text »
The Rat Glucocorticoid Receptor Mutant K461A Differentiates between Two Different Mechanisms of Transrepression.
T. Meyer, D. B. Starr, and J. Carlstedt-Duke (1997)
J. Biol. Chem. 272, 21090-21095
   Abstract »    Full Text »    PDF »
Polarity and Specific Sequence Requirements of Peroxisome Proliferator-activated Receptor (PPAR)/Retinoid X Receptor Heterodimer Binding to DNA. A FUNCTIONAL ANALYSIS OF THE MALIC ENZYME GENE PPAR RESPONSE ELEMENT.
A. IJpenberg, E. Jeannin, W. Wahli, and B. Desvergne (1997)
J. Biol. Chem. 272, 20108-20117
   Abstract »    Full Text »    PDF »
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.
D. S. Sem, D. R. Casimiro, S. A. Kliewer, J. Provencal, R. M. Evans, and P. E. Wright (1997)
J. Biol. Chem. 272, 18038-18043
   Abstract »    Full Text »    PDF »
Androgen and Glucocorticoid Receptor Heterodimer Formation. A POSSIBLE MECHANISM FOR MUTUAL INHIBITION OF TRANSCRIPTIONAL ACTIVITY.
S.-y. Chen, J. Wang, G.-q. Yu, W. Liu, and D. Pearce (1997)
J. Biol. Chem. 272, 14087-14092
   Abstract »    Full Text »    PDF »
Thyroid Hormone-mediated Enhancement of Heterodimer Formation between Thyroid Hormone Receptor beta  and Retinoid X Receptor.
T. N. Collingwood, A. Butler, Y. Tone, R. J. Clifton-Bligh, M. G. Parker, and V. K. K. Chatterjee (1997)
J. Biol. Chem. 272, 13060-13065
   Abstract »    Full Text »    PDF »
alpha -Helical Protein Assembly Motifs.
W. D. Kohn, C. T. Mant, and R. S. Hodges (1997)
J. Biol. Chem. 272, 2583-2586
   Full Text »    PDF »
DNA Intersegment Transfer, How Steroid Receptors Search for A Target Site.
B. A. Lieberman and S. K. Nordeen (1997)
J. Biol. Chem. 272, 1061-1068
   Abstract »    Full Text »    PDF »
Function of Directly Repeated Half-sites as Response Elements for Steroid Hormone Receptors.
J. P. Aumais, H. S. Lee, C. DeGannes, J. Horsford, and J. H. White (1996)
J. Biol. Chem. 271, 12568-12577
   Abstract »    Full Text »    PDF »
Intracellular receptors use a common mechanism to interpret signaling information at response elements..
D B Starr, W Matsui, J R Thomas, and K R Yamamoto (1996)
Genes & Dev. 10, 1271-1283
   Abstract »    PDF »
The Ligand Binding Domain of the Human Retinoic Acid Receptor [IMAGE] Is Predominantly alpha-Helical with a Trp Residue in the Ligand Binding Site.
J. A. Lupisella, J. E. Driscoll, W. J. Metzler, and P. R. Reczek (1995)
J. Biol. Chem. 270, 24884-24890
   Abstract »    Full Text »    PDF »
Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A.
T Tsukihara, H Aoyama, E Yamashita, T Tomizaki, H Yamaguchi, K Shinzawa-Itoh, R Nakashima, R Yaono, and S Yoshikawa (1995)
Science 269, 1069-1074
   Abstract »    PDF »
Relationship between P-box Amino Acid Sequence and DNA Binding Specificity of the Thyroid Hormone Receptor.
C. C. Nelson, S. C. Hendy, and P. J. Romaniuk (1995)
J. Biol. Chem. 270, 16981-16987
   Abstract »    Full Text »    PDF »
Influence of a steroid receptor DNA-binding domain on transcriptional regulatory functions..
J A Lefstin, J R Thomas, and K R Yamamoto (1994)
Genes & Dev. 8, 2842-2856
   Abstract »    PDF »
Coupling of local folding to site-specific binding of proteins to DNA.
R. Spolar and M. Record Jr (1994)
Science 263, 777-784
   Abstract »    PDF »
NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1.
J. Omichinski, G. Clore, O Schaad, G Felsenfeld, C Trainor, E Appella, S. Stahl, and A. Gronenborn (1993)
Science 261, 438-446
   Abstract »    PDF »
Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding.
M. Lee, S. Kliewer, J Provencal, P. Wright, and R. Evans (1993)
Science 260, 1117-1121
   Abstract »    PDF »
Participation of non-zinc finger residues in DNA binding by two nuclear orphan receptors.
T. Wilson, R. Paulsen, K. Padgett, and J Milbrandt (1992)
Science 256, 107-110
   Abstract »    PDF »
Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A.
N. Pavletich and C. Pabo (1991)
Science 252, 809-817
   Abstract »    PDF »
FTZ-F1, a steroid hormone receptor-like protein implicated in the activation of fushi tarazu.
G Lavorgna, H Ueda, J Clos, and C Wu (1991)
Science 252, 848-851
   Abstract »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)