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Structural Analysis of Heterodimeric Nuclear Receptors

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Nuclear Receptors: From Structure to the Clinic

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Abstract

Nuclear receptors are ligand dependent transcription factors that control gene expression by coordinating protein assemblies. Their modular organization confers the necessary flexibility to adapt their conformation to multiple different partners. They either function as homo or heterodimers with a common partner (RXR in vertebrates). The present chapter deals with the large subgroup of heterodimers for which seven solution structures and two crystal structures of DNA bound receptors are presently available. The results show the molecular architecture of the complexes and illustrate the adaptability of the receptors while revealing some common features like their L-shape open conformation with an asymmetric position of the ligand binding domains. The structural data enlighten the important role of the promoter and the protein hinges into the spatial organization of the DNA and ligand binding domains. They explain how DNA dictates the topology of the complex and its asymmetry, thus remodeling the interaction surfaces according to the different response elements. The structural investigations provide additional information related to the dynamics of the regulation process like the solution structure of the free RARα/RXRα heterodimer, the binding mode of protein cofactors and the stoichiometry of the resulting complexes.

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Authors and Affiliations

  1. Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, Illkirch, France

    Brice Beinsteiner & Dino Moras

  2. Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Illkirch, France

    Brice Beinsteiner & Dino Moras

  3. Centre National de la Recherche Scientifique (CNRS) UMR 7104, Illkirch, France

    Brice Beinsteiner & Dino Moras

  4. Université de Strasbourg, Strasbourg, France

    Brice Beinsteiner & Dino Moras

Authors
  1. Brice Beinsteiner
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  2. Dino Moras
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Correspondence to Dino Moras .

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Editors and Affiliations

  1. School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

    Iain J. McEwan

  2. Department of Basic Sciences, The Commonwealth Medical College, Scranton, Pennsylvania, USA

    Raj Kumar

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Beinsteiner, B., Moras, D. (2015). Structural Analysis of Heterodimeric Nuclear Receptors. In: McEwan, I., Kumar, R. (eds) Nuclear Receptors: From Structure to the Clinic. Springer, Cham. https://doi.org/10.1007/978-3-319-18729-7_7

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