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| Subject Categories: Chromatin & Transcription | Structural Biology |
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| The EMBO Journal
(2007) 26, 3770–3782, doi:10.1038/sj.emboj.7601810 Published online 2 August 2007 |
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| Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor |
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| Thomas Iwema1, 5, 6, Isabelle ML Billas1, 5, Yannick Beck1, François Bonneton2, Hélène Nierengarten1, Arnaud Chaumot2, 3, Geoff Richards4, Vincent Laudet2 and Dino Moras1 |
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1 IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), (UMR7104 CNRS, U596 INSERM, ULP), Département de Biologie et de Génomique Structurales, Illkirch, France 2 Université de Lyon, Université Lyon 1, Ecole Normale Supérieure de Lyon, IGFL, CNRS UMR5242, INRA UMR1237, IFR128, Lyon, France 3 CEMAGREF, Laboratoire d'Ecotoxicologie, Lyon Cedex, France 4 HFSP (Human Frontier Science Program), Strasbourg, France To whom correspondence should be addressed Dino Moras, Laboratoire de Biologie et Génomique Structurales, IGBMC UMR7104, 1 rue Laurent Fries, BP 10142, Illkirch 67404, France. Tel.: +33 388 653 220; Fax: +33 388 653 276; E-mail: moras@igbmc.u-strasbg.fr Vincent Laudet, Université de Lyon, Ecole Normale Supérieure de Lyon, LBMC, CNRS UMR5161, INRA UMR1237, IFR128, 46 Allée d'Italie, Lyon Cedex 07 69364, France. Tel.: +33 472 728 190; Fax: +33 472 728 080; E-mail: vincent.laudet@ens-lyon.fr 5 These authors contributed equally to this work 6 Present address: IBS (Institut de Biologie Structurale), LCCP, 41, rue Jules Horowitz, 38027 Grenoble Cedex 1, France Received 30 January 2007; Accepted 2 July 2007; Published online 2 August 2007. |
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| Abstract |
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| Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor–ligand binding evolution and dynamics. |
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| Keywords: constitutive activity, ligand binding, nuclear receptor, retinoid X receptor, ultraspiracle |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHStructural and functional characterization of a novel type of ligand-independent RXR-USP receptor The EMBO Journal Article Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor Nature Letters to Editor (06 Nov 2003) Structure of the heterodimeric ecdysone receptor DNA-binding complex The EMBO Journal Article (03 Nov 2003) |
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