The dioxin receptor is a cytoplasmic basic helix-loop-helix/Per-Arnt-Sim homology (bHLH/PAS) protein known to bind planar polycyclic ligands including polycyclic aromatic hydrocarbons, benzoflavones, heterocyclic amines, and halogenated aromatic hydrocarbons, e.g. dioxins. Ligand-induced activation of the dioxin receptor initiates a process whereby the receptor is transformed into a nuclear transcription factor complex with a specific bHLH/PAS partner protein, Arnt. In analogy to the glucocorticoid receptor, the latent dioxin receptor is found associated with the molecular chaperone hsp90. We have defined and isolated a minimal ligand binding domain of the dioxin receptor from the central PAS region, comprising of amino acids 230 to 421, and found this domain to interact with hsp90 in vitro. Expression of the minimal ligand binding domain in wheat germ lysates or bacteria, systems which harbor hsp90 homologs unable to interact with the glucocorticoid or dioxin receptors, resulted in non-ligand binding forms of this minimal 230 to 421 fragment. Importantly, affinity of the minimal ligand binding domain for dioxin was similar to the affinity inherent in the full-length dioxin receptor, and a profile of ligand structures which specifically bound the minimal ligand binding domain was found to be conserved between this domain and the native receptor. These experiments show that the minimal ligand binding domain maintains the quantitative and qualitative aspects of ligand binding exhibited by the full-length receptor, implying that the central ligand binding pocket may exist to accommodate all classes of specific dioxin receptor ligands, and that this pocket is critically dependent upon hsp90 for its ligand binding conformation.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. Soshilov and M. S. Denison Role of the Per/Arnt/Sim Domains in Ligand-dependent Transformation of the Aryl Hydrocarbon Receptor J. Biol. Chem., November 21, 2008; 283(47): 32995 - 33005. [Abstract] [Full Text] [PDF]

				H. Sekine, J. Mimura, M. Yamamoto, and Y. Fujii-Kuriyama Unique and Overlapping Transcriptional Roles of Arylhydrocarbon Receptor Nuclear Translocator (Arnt) and Arnt2 in Xenobiotic and Hypoxic Responses J. Biol. Chem., December 8, 2006; 281(49): 37507 - 37516. [Abstract] [Full Text] [PDF]

				T.-S. Kim, C.-Y. Jang, H. D. Kim, J. Y. Lee, B.-Y. Ahn, and J. Kim Interaction of Hsp90 with Ribosomal Proteins Protects from Ubiquitination and Proteasome-dependent Degradation Mol. Biol. Cell, February 1, 2006; 17(2): 824 - 833. [Abstract] [Full Text] [PDF]

				J. A. Lavine, A. J. Rowatt, T. Klimova, A. J. Whitington, E. Dengler, C. Beck, and W. H. Powell Aryl Hydrocarbon Receptors in the Frog Xenopus laevis: Two AhR1 Paralogs Exhibit Low Affinity for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Toxicol. Sci., November 1, 2005; 88(1): 60 - 72. [Abstract] [Full Text] [PDF]

				Q. Ma, F. Roy, S. Herrmann, B. L. Taylor, and M. S. Johnson The Aer Protein of Escherichia coli Forms a Homodimer Independent of the Signaling Domain and Flavin Adenine Dinucleotide Binding J. Bacteriol., November 1, 2004; 186(21): 7456 - 7459. [Abstract] [Full Text] [PDF]

				S. Herrmann, Q. Ma, M. S. Johnson, A. V. Repik, and B. L. Taylor PAS Domain of the Aer Redox Sensor Requires C-Terminal Residues for Native-Fold Formation and Flavin Adenine Dinucleotide Binding J. Bacteriol., October 15, 2004; 186(20): 6782 - 6791. [Abstract] [Full Text] [PDF]

				A. Chapman-Smith, J. K. Lutwyche, and M. L. Whitelaw Contribution of the Per/Arnt/Sim (PAS) Domains to DNA Binding by the Basic Helix-Loop-Helix PAS Transcriptional Regulators J. Biol. Chem., February 13, 2004; 279(7): 5353 - 5362. [Abstract] [Full Text] [PDF]

				M. Backlund and M. Ingelman-Sundberg Different Structural Requirements of the Ligand Binding Domain of the Aryl Hydrocarbon Receptor for High- and Low-Affinity Ligand Binding and Receptor Activation Mol. Pharmacol., February 1, 2004; 65(2): 416 - 425. [Abstract] [Full Text] [PDF]

				M. J. Lees, D. J. Peet, and M. L. Whitelaw Defining the Role for XAP2 in Stabilization of the Dioxin Receptor J. Biol. Chem., September 19, 2003; 278(38): 35878 - 35888. [Abstract] [Full Text] [PDF]

				Y. Kikuchi, S. Ohsawa, J. Mimura, M. Ema, C. Takasaki, K. Sogawa, and Y. Fujii-Kuriyama Heterodimers of bHLH-PAS Protein Fragments Derived from AhR, AhRR, and Arnt Prepared by Co-Expression in Escherichia coli: Characterization of Their DNA Binding Activity and Preparation of a DNA Complex J. Biochem., July 1, 2003; 134(1): 83 - 90. [Abstract] [Full Text] [PDF]

				E. Hur, H.-H. Kim, S. M. Choi, J. H. Kim, S. Yim, H. J. Kwon, Y. Choi, D. K. Kim, M.-O. Lee, and H. Park Reduction of Hypoxia-Induced Transcription through the Repression of Hypoxia-Inducible Factor-1alpha /Aryl Hydrocarbon Receptor Nuclear Translocator DNA Binding by the 90-kDa Heat-Shock Protein Inhibitor Radicicol Mol. Pharmacol., November 1, 2002; 62(5): 975 - 982. [Abstract] [Full Text] [PDF]

				P. Berg and I. Pongratz Two Parallel Pathways Mediate Cytoplasmic Localization of the Dioxin (Aryl Hydrocarbon) Receptor J. Biol. Chem., August 23, 2002; 277(35): 32310 - 32319. [Abstract] [Full Text] [PDF]

				J. S. Isaacs, Y.-J. Jung, E. G. Mimnaugh, A. Martinez, F. Cuttitta, and L. M. Neckers Hsp90 Regulates a von Hippel Lindau-independent Hypoxia-inducible Factor-1alpha -degradative Pathway J. Biol. Chem., August 9, 2002; 277(33): 29936 - 29944. [Abstract] [Full Text] [PDF]

				E. A. Andreasen, M. E. Hahn, W. Heideman, R. E. Peterson, and R. L. Tanguay The Zebrafish (Danio rerio) Aryl Hydrocarbon Receptor Type 1 Is a Novel Vertebrate Receptor Mol. Pharmacol., August 1, 2002; 62(2): 234 - 249. [Abstract] [Full Text] [PDF]

				E. A. Andreasen, R. L. Tanguay, R. E. Peterson, and W. Heideman Identification of a Critical Amino Acid in the Aryl Hydrocarbon Receptor J. Biol. Chem., April 5, 2002; 277(15): 13210 - 13218. [Abstract] [Full Text] [PDF]

				J. McGuire, K. Okamoto, M. L. Whitelaw, H. Tanaka, and L. Poellinger Definition of a Dioxin Receptor Mutant That Is a Constitutive Activator of Transcription. DELINEATION OF OVERLAPPING REPRESSION AND LIGAND BINDING FUNCTIONS WITHIN THE PAS DOMAIN J. Biol. Chem., November 2, 2001; 276(45): 41841 - 41849. [Abstract] [Full Text] [PDF]

				C. J. Elferink, N.-L. Ge, and A. Levine Maximal Aryl Hydrocarbon Receptor Activity Depends on an Interaction with the Retinoblastoma Protein Mol. Pharmacol., April 1, 2001; 59(4): 664 - 673. [Abstract] [Full Text]

				Regulations and Advisories Toxicology and Industrial Health, April 1, 2000; 16(3-5): 173 - 201. [PDF]

				A. Puga, S. J. Barnes, T. P. Dalton, C.-y. Chang, E. S. Knudsen, and M. A. Maier Aromatic Hydrocarbon Receptor Interaction with the Retinoblastoma Protein Potentiates Repression of E2F-dependent Transcription and Cell Cycle Arrest J. Biol. Chem., January 28, 2000; 275(4): 2943 - 2950. [Abstract] [Full Text] [PDF]

				A. Voss, T Thomas, and P Gruss Mice lacking HSP90beta fail to develop a placental labyrinth Development, January 1, 2000; 127(1): 1 - 11. [Abstract] [PDF]

				M. J. Lees and M. L. Whitelaw Multiple Roles of Ligand in Transforming the Dioxin Receptor to an Active Basic Helix-Loop-Helix/PAS Transcription Factor Complex with the Nuclear Protein Arnt Mol. Cell. Biol., August 1, 1999; 19(8): 5811 - 5822. [Abstract] [Full Text] [PDF]

				B. L. Taylor and I. B. Zhulin PAS Domains: Internal Sensors of Oxygen, Redox Potential, and Light Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 479 - 506. [Abstract] [Full Text] [PDF]

				L. A. Carver, J. J. LaPres, S. Jain, E. E. Dunham, and C. A. Bradfield Characterization of the Ah Receptor-associated Protein, ARA9 J. Biol. Chem., December 11, 1998; 273(50): 33580 - 33587. [Abstract] [Full Text] [PDF]

				J.-F. Louvion, T. Abbas-Terki, and D. Picard Hsp90 Is Required for Pheromone Signaling in Yeast Mol. Biol. Cell, November 1, 1998; 9(11): 3071 - 3083. [Abstract] [Full Text]

				H. I. Swanson and J.-H. Yang The Aryl Hydrocarbon Receptor Interacts with Transcription Factor IIB Mol. Pharmacol., October 1, 1998; 54(4): 671 - 677. [Abstract] [Full Text]

				I. Pongratz, C. Antonsson, M. L. Whitelaw, and L. Poellinger Role of the PAS Domain in Regulation of Dimerization and DNA Binding Specificity of the Dioxin Receptor Mol. Cell. Biol., July 1, 1998; 18(7): 4079 - 4088. [Abstract] [Full Text]

				J. A. Powell-Coffman, C. A. Bradfield, and W. B. Wood Caenorhabditis elegans orthologs of the aryl hydrocarbon receptor and its heterodimerization partner the aryl hydrocarbon receptor nuclear translocator PNAS, March 17, 1998; 95(6): 2844 - 2849. [Abstract] [Full Text] [PDF]

				S. T. Crews Control of cell lineage-specific development and transcription by bHLH-PAS proteins Genes & Dev., March 1, 1998; 12(5): 607 - 620. [Full Text]

				M. E. Hahn, S. I. Karchner, M. A. Shapiro, and S. A. Perera Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family PNAS, December 9, 1997; 94(25): 13743 - 13748. [Abstract] [Full Text] [PDF]

				W. B. Pratt and D. O. Toft Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones Endocr. Rev., June 1, 1997; 18(3): 306 - 360. [Abstract] [Full Text]

				N. Dzeletovic, J. McGuire, M. Daujat, J. Tholander, M. Ema, Y. Fujii-Kuriyama, J. Bergman, P. Maurel, and L. Poellinger Regulation of Dioxin Receptor Function by Omeprazole J. Biol. Chem., May 9, 1997; 272(19): 12705 - 12713. [Abstract] [Full Text] [PDF]

				Y.-D. Zhou, M. Barnard, H. Tian, X. Li, H. Z. Ring, U. Francke, J. Shelton, J. Richardson, D. W. Russell, and S. L. McKnight Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system PNAS, January 21, 1997; 94(2): 713 - 718. [Abstract] [Full Text] [PDF]

				D. R. Bell and A. Poland Binding of Aryl Hydrocarbon Receptor (AhR) to AhR-interacting Protein. THE ROLE OF hsp90 J. Biol. Chem., November 10, 2000; 275(46): 36407 - 36414. [Abstract] [Full Text] [PDF]