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Architecture of DNA Bound RAR Heterodimers

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The Biochemistry of Retinoic Acid Receptors I: Structure, Activation, and Function at the Molecular Level

Part of the book series: Subcellular Biochemistry ((SCBI,volume 70))

Abstract

Nuclear Retinoic Acid receptors (RARs) consist of three subtypes, α, β, and γ, encoded by separate genes. They function as ligand-dependent transcriptional regulators, forming heterodimers with Retinoid X receptors (RXRs). RARs mediate the effects of retinoic acid (RA), the active metabolite of Vitamin A, and regulate many biological functions such as embryonic development, organogenesis, homeostasis, vision, immune functions, and reproduction. During the two last decades, a number of in-depth structure–function relationship studies have been performed, in particular with drug design perspectives in the therapeutics for cancer, dermatology, metabolic disease, and other human diseases. Recent structural results concerning integral receptors in diverse functional states, obtained using a combination of different methods, allow a better understanding of the mechanisms involved in molecular regulation. The structural data highlight the importance of DNA sequences for binding selectivity and the role of promoter response elements in the spatial organization of the protein domains into functional complexes.

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Abbreviations

AF-1:

Activation function 1

AF-2:

Activation function 2

ChIP:

Chromatin immuno-precipitation

DBD:

DNA binding domain

DR:

Direct repeat

Cryo-EM:

Cryo-electron microscopy

FRET:

Fluorescence resonance energy transfer

GR:

Glucocorticoid receptor

HDX:

Hydrogen deuterium exchange

IR:

Inverted repeat

LBD:

Ligand binding domain

LBP:

Ligand binding pocket

NR:

Nuclear receptor

NTD:

N-terminal domain

PPAR:

Peroxisome proliferator-activated receptor

RA:

All-trans retinoic acid

RAR:

Retinoic acid nuclear receptor

RARE:

Retinoic acid nuclear receptor response element

RXR:

Retinoid X nuclear receptor

SANS:

Small angle neutron scattering

SAXS:

Small angle X-ray scattering

VDR:

Vitamin D nuclear receptor

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Authors and Affiliations

  1. Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM), U964, Centre National de Recherche Scientifique (CNRS), UMR7104, Université de Strasbourg, 67404, Illkirch, France

    Natacha Rochel & Dino Moras

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  1. Natacha Rochel
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  2. Dino Moras
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Correspondence to Natacha Rochel or Dino Moras .

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Editors and Affiliations

  1. Department of Biological Sciences, Tennessee State University, Nashville, Tennessee, USA

    Mary Ann Asson-Batres

  2. IGBMC, Illkirch Cedex, France

    Cécile Rochette-Egly

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Rochel, N., Moras, D. (2014). Architecture of DNA Bound RAR Heterodimers. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoic Acid Receptors I: Structure, Activation, and Function at the Molecular Level. Subcellular Biochemistry, vol 70. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9050-5_2

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