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Structure of the heterodimeric ecdysone receptor DNA-binding complex.

Devarakonda S, Harp JM, Kim Y, Ozyhar A, Rastinejad F
EMBO J 22 5827-40 (2003)
Cited: 53 times
EuropePMC logo PMID: 14592980

Abstract

Ecdysteroids initiate molting and metamorphosis in insects via a heterodimeric receptor consisting of the ecdysone receptor (EcR) and ultraspiracle (USP). The EcR-USP heterodimer preferentially mediates transcription through highly degenerate pseudo-palindromic response elements, resembling inverted repeats of 5'-AGGTCA-3' separated by 1 bp (IR-1). The requirement for a heterodimeric arrangement of EcR-USP subunits to bind to a symmetric DNA is unusual within the nuclear receptor superfamily. We describe the 2.24 A structure of the EcR-USP DNA-binding domain (DBD) heterodimer bound to an idealized IR-1 element. EcR and USP use similar surfaces, and rely on the deformed minor groove of the DNA to establish protein-protein contacts. As retinoid X receptor (RXR) is the mammalian homolog of USP, we also solved the 2.60 A crystal structure of the EcR-RXR DBD heterodimer on IR-1 and found the dimerization and DNA-binding interfaces to be the same as in the EcR-USP complex. Sequence alignments indicate that the EcR-RXR heterodimer is an important model for understanding how the FXR-RXR heterodimer binds to IR-1 sites.

Reviews - 1r0o mentioned but not cited (2)

  1. The retinoid X receptors and their ligands. Dawson MI, Xia Z. Biochim Biophys Acta 1821 21-56 (2012)
  2. Farnesoid X receptor (FXR): Structures and ligands. Jiang L, Zhang H, Xiao D, Wei H, Chen Y. Comput Struct Biotechnol J 19 2148-2159 (2021)

Articles - 1r0o mentioned but not cited (6)



Reviews citing this publication (9)

  1. Arthropod nuclear receptors and their role in molting. Nakagawa Y, Henrich VC. FEBS J 276 6128-6157 (2009)
  2. Gene therapy progress and prospects: transcription regulatory systems. Toniatti C, Bujard H, Cortese R, Ciliberto G. Gene Ther 11 649-657 (2004)
  3. Understanding nuclear receptor form and function using structural biology. Rastinejad F, Huang P, Chandra V, Khorasanizadeh S. J Mol Endocrinol 51 T1-T21 (2013)
  4. Retinoic acid actions through mammalian nuclear receptors. Huang P, Chandra V, Rastinejad F. Chem Rev 114 233-254 (2014)
  5. Ecdysone receptors: from the Ashburner model to structural biology. Hill RJ, Billas IM, Bonneton F, Graham LD, Lawrence MC. Annu Rev Entomol 58 251-271 (2013)
  6. Ecdysteroid hormone action. Spindler KD, Hönl C, Tremmel Ch, Braun S, Ruff H, Spindler-Barth M. Cell Mol Life Sci 66 3837-3850 (2009)
  7. Drosophila nutrigenomics can provide clues to human gene-nutrient interactions. Ruden DM, De Luca M, Garfinkel MD, Bynum KL, Lu X. Annu Rev Nutr 25 499-522 (2005)
  8. Structural analysis of nuclear receptors: from isolated domains to integral proteins. Brélivet Y, Rochel N, Moras D. Mol Cell Endocrinol 348 466-473 (2012)
  9. Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders. Appelman MD, van der Veen SW, van Mil SWC. Front Endocrinol (Lausanne) 12 729828 (2021)

Articles citing this publication (36)



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