Rochel N.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire |
Rochel N.,Institute National Of Sante Et Of Recherche Medicale U964 |
Rochel N.,French National Center for Scientific Research |
Rochel N.,University of Strasbourg |
And 27 more authors.
Nature Structural and Molecular Biology | Year: 2011
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 5-2 ends of the target DNAs and the binding of only one coactivator molecule per heterodimer, to RXR's partner. © 2011 Nature America, Inc. All rights reserved.