title: Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings.
abstract: Nuclear hormone receptors (NHRs) control numerous physiological processes through the regulation of gene expression. The present study provides a structural basis for understanding the role of DNA in the spatial organization of NHR heterodimers in complexes with coactivators such as Med1 and SRC-1. We have used SAXS, SANS and FRET to determine the solution structures of three heterodimer NHR complexes (RXR-RAR, PPAR-RXR and RXR-VDR) coupled with the NHR interacting domains of coactivators bound to their cognate direct repeat elements. The structures show an extended asymmetric shape and point to the important role played by the hinge domains in establishing and maintaining the integrity of the structures. The results reveal two additional features: the conserved position of the ligand-binding domains at the 5' ends of the target DNAs and the binding of only one coactivator molecule per heterodimer, to RXR's partner.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. rochel@igbmc.fr
authors.forename: Natacha
authors.initials: N
authors.lastname: Rochel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Ciesielski
authors.forename: Julien
authors.initials: J
authors.lastname: Godet
authors.forename: Edelmiro
authors.initials: E
authors.lastname: Moman
authors.forename: Manfred
authors.initials: M
authors.lastname: Roessle
authors.forename: Carole
authors.initials: C
authors.lastname: Peluso-Iltis
authors.forename: Martine
authors.initials: M
authors.lastname: Moulin
authors.forename: Michael
authors.initials: M
authors.lastname: Haertlein
authors.forename: Phil
authors.initials: P
authors.lastname: Callow
authors.forename: Yves
authors.initials: Y
authors.lastname: Mély
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Dino
authors.initials: D
authors.lastname: Moras
mesh_terms: D001665:Binding Sites; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D047495:PPAR gamma / Q000737:chemistry*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D012091:Repetitive Sequences, Nucleic Acid; D047490:Retinoid X Receptor alpha / Q000737:chemistry*; D053838:Scattering, Small Angle
chemical_list: D008024:Ligands; D047495:PPAR gamma; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D047490:Retinoid X Receptor alpha