Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA

Nature Structural and Molecular Biology

Volumn 21, Issue 3, 2014, Pages 277-281

  Lou, Xiaohua ^a,b   Toresson, Gudrun ^c   Benod, Cindy ^a,b   Suh, Ji Ho ^b   Philips, Kevin J ^b   Webb, Paul ^a,b   Gustafsson, Jan Ake ^a,c  

^a University of Houston   (United States)

^b HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^c KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; HETERODIMER; LIVER X RECEPTOR BETA; NUCLEAR RECEPTOR COACTIVATOR 2; RETINOID X RECEPTOR ALPHA;

AMINO TERMINAL SEQUENCE; ARTICLE; CRYSTAL STRUCTURE; HUMAN; LIGAND BINDING; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN STRUCTURE; X RAY DIFFRACTION; ZINC FINGER MOTIF;

DNA; DNA, COMPLEMENTARY; ESCHERICHIA COLI; HUMANS; LIGANDS; MODELS, MOLECULAR; MUTATION; ORPHAN NUCLEAR RECEPTORS; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; RETINOID X RECEPTOR ALPHA; ZINC FINGERS;

EID: 84895886993     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.2778     Document Type: Article

References (49)

1. Evans, R.M. The nuclear receptor superfamily: A Rosetta Stone for physiology. Mol. Endocrinol. 19, 1429-1438 (2005
2. Chawla, A., Repa, J.J., Evans, R.M. & Mangelsdorf, D.J. Nuclear receptors and lipid physiology: Opening the X-files. Science 294, 1866-1870 (2001
3. Kliewer, S.A., Lehmann, J.M. & Willson, T.M. Orphan nuclear receptors: Shifting endocrinology into reverse. Science 284, 757-760 (1999
4. Huang, P., Chandra, V. & Rastinejad, F. Structural overview of the nuclear receptor superfamily: Insights into physiology and therapeutics. Annu. Rev. Physiol. 72, 247-272 (2010
5. Chandra, V. et al. Structure of the intact PPAR-γ-RXR-α nuclear receptor complex on DNA. Nature 456, 350-356 (2008
6. Chandra, V. et al. Multidomain integration in the structure of the HNF-4α nuclear receptor complex. Nature 495, 394-398 (2013
7. Repa, J.J. et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ. Genes Dev. 14, 2819-2830 (2000
8. Gerin, I. et al. LXRβ is required for adipocyte growth, glucose homeostasis, and β cell function. J. Biol. Chem. 280, 23024-23031 (2005
9. Kalaany, N.Y. et al. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 1, 231-244 (2005
10. Korach-André, M. et al. Separate and overlapping metabolic functions of LXRα and LXRβ in C57Bl/6 female mice. Am. J. Physiol. Endocrinol. Metab. 298, E167-E178 (2010
11. Korach-André, M., Archer, A., Barros, R.P., Parini, P. & Gustafsson, J-Å. Both liver-X receptor (LXR) isoforms control energy expenditure by regulating brown adipose tissue activity. Proc. Natl. Acad. Sci. USA 108, 403-408 (2011
12. Steffensen, K.R. et al. Genome-wide expression profiling; a panel of mouse tissues discloses novel biological functions of liver X receptors in adrenals. J. Mol. Endocrinol. 33, 609-622 (2004
13. Venteclef, N. et al. GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRβ in the hepatic acute phase response. Genes Dev. 24, 381-395 (2010
14. Blaschke, F. et al. A nuclear receptor corepressor-dependent pathway mediates suppression of cytokine-induced C-reactive protein gene expression by liver X receptor. Circ. Res. 99, e88-e99 (2006
15. Koldamova, R., Fitz, N.F. & Lefterov, I. The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration. Biochim. Biophys. Acta 1801, 824-830 (2010
16. Saijo, K., Crotti, A. & Glass, C.K. in Advances in Immunology, Vol. 106 (ed. Frederick W. Alt) 21-59 (Academic Press, 2010
17. Hindinger, C. et al. Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis. J. Neurosci. Res. 84, 1225-1234 (2006
18. Xu, J., Wagoner, G., Douglas, J.C. & Drew, P.D. Liver X receptor agonist regulation of Th17 lymphocyte function in autoimmunity. J. Leukoc. Biol. 86, 401-409 (2009
19. Cui, G. et al. Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J. Clin. Invest. 121, 658-670 (2011
20. Wang, L. et al. Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration. Proc. Natl. Acad. Sci. USA 99, 13878-13883 (2002
21. Cermenati, G. et al. Activation of the liver X receptor increases neuroactive steroid levels and protects from diabetes-induced peripheral neuropathy. J. Neurosci. 30, 11896-11901 (2010
22. Nguyen-Vu, T. et al. Liver X receptor ligands disrupt breast cancer cell proliferation through an E2F-mediated mechanism. Breast Cancer Res. 15, R51 (2013
23. Lo Sasso, G. et al. Liver X receptors inhibit proliferation of human colorectal cancer cells and growth of intestinal tumors in mice. Gastroenterology 144, 1497-1507 (2013
24. Gabbi, C. et al. Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β. Proc. Natl. Acad. Sci. USA 109, 3030-3034 (2012
25. Gabbi, C. et al. Pancreatic exocrine insufficiency in LXRβ-/- mice is associated with a reduction in aquaporin-1 expression. Proc. Natl. Acad. Sci. USA 105, 15052-15057 (2008
26. Fan, X., Kim, H-J., Bouton, D., Warner, M. & Gustafsson, J-A. Expression of liver X receptor β is essential for formation of superficial cortical layers and migration of later-born neurons. Proc. Natl. Acad. Sci. USA 105, 13445-13450 (2008
27. Kim, H-J. et al. Liver X receptor β (LXRβ): A link between β-sitosterol and amyotrophic lateral sclerosis-Parkinson's dementia. Proc. Natl. Acad. Sci. USA 105, 2094-2099 (2008
28. Sacchetti, P. et al. Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells. Cell Stem Cell 5, 409-419 (2009
29. Dai, Y.B., Tan, X.J., Wu, W.F., Warner, M. & Gustafsson, J-A. Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease. Proc. Natl. Acad. Sci. USA 109, 13112-13117 (2012
30. Jakobsson, T., Treuter, E., Gustafsson, J-Å. & Steffensen, K.R. Liver X receptor biology and pharmacology: New pathways, challenges and opportunities. Trends Pharmacol. Sci. 33, 394-404 (2012
31. Umesono, K., Murakami, K.K., Thompson, C.C. & Evans, R.M. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65, 1255-1266 (1991
32. Yoshinari, K., Ohno, H., Benoki, S. & Yamazoe, Y. Constitutive androstane receptor transactivates the hepatic expression of mouse Dhcr24 and human DHCR24 encoding a cholesterogenic enzyme 24-dehydrocholesterol reductase. Toxicol. Lett. 208, 185-191 (2012
33. Echchgadda, I. et al. The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4α in the regulation of human steroid-/bile acid-sulfotransferase. Mol. Endocrinol. 21, 2099-2111 (2007
34. Laffitte, B.A. et al. Identification of the DNA binding specificity and potential target genes for the farnesoid X-Activated receptor. J. Biol. Chem. 275, 10638-10647 (2000
35. Stroup, D., Crestani, M. & Chiang, J.Y.L. Orphan receptors chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and retinoid X receptor (RXR) activate and bind the rat cholesterol 7α-hydroxylase gene (CYP7A). J. Biol. Chem. 272, 9833-9839 (1997
36. Khorasanizadeh, S. & Rastinejad, F. Nuclear-receptor interactions on DNA-response elements. Trends Biochem. Sci. 26, 384-390 (2001
37. Orlov, I., Rochel, N., Moras, D. & Klaholz, B.P. Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA. EMBO J. 31, 291-300 (2012
38. Rochel, N. et al. Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings. Nat. Struct. Mol. Biol. 18, 564-570 (2011
39. Bernardes, A. et al. Low-resolution molecular models reveal the oligomeric state of the PPAR and the conformational organization of its domains in solution. PLoS ONE 7, e31852 (2012
40. Fischer, H. et al. 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 (2003
41. Figueira, A.C.M. et al. Low-resolution structures of thyroid hormone receptor dimers and tetramers in solution. Biochemistry 46, 1273-1283 (2007
42. Shulman, A.I., Larson, C., Mangelsdorf, D.J. & Ranganathan, R. Structural determinants of allosteric ligand activation in RXR heterodimers. Cell 116, 417-429 (2004
43. Nettles, K.W. & Greene, G.L. Ligand control of coregulator recruitment to nuclear receptors. Annu. Rev. Physiol. 67, 309-333 (2005
44. Rastinejad, F., Perlmann, T., Evans, R.M. & Sigler, P.B. Structural determinants of nuclear receptor assembly on DNA direct repeats. Nature 375, 203-211 (1995
45. Kurokawa, R. et al. Differential orientations of the DNA-binding domain and carboxy-terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers. Genes Dev. 7, 1423-1435 (1993
46. Wrange, O. & Gustafsson, J.A. Separation of the hormone- and DNA-binding sites of the hepatic glucocorticoid receptor by means of proteolysis. J. Biol. Chem. 253, 856-865 (1978
47. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997
48. Chao, E.Y. et al. Structure-guided design of n-phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity. J. Med. Chem. 51, 5758-5765 (2008
49. Adams, P.D. et al. PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010.