Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings

被引:140
作者
Rochel, Natacha [1 ,2 ,3 ,4 ]
Ciesielski, Fabrice [1 ,2 ,3 ,4 ]
Godet, Julien [4 ,5 ,6 ]
Moman, Edelmiro [1 ,2 ,3 ,4 ]
Roessle, Manfred [7 ]
Peluso-Iltis, Carole [1 ,2 ,3 ,4 ]
Moulin, Martine [8 ]
Haertlein, Michael [8 ]
Callow, Phil [8 ]
Mely, Yves [4 ,5 ,6 ]
Svergun, Dmitri I. [7 ]
Moras, Dino [1 ,2 ,3 ,4 ]
机构
[1] Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France
[2] INSERM, U964, Illkirch Graffenstaden, France
[3] CNRS, UMR 7104, Illkirch Graffenstaden, France
[4] Univ Strasbourg, Illkirch Graffenstaden, France
[5] Fac Pharm, Lab Biophoton & Pharmacol, Illkirch Graffenstaden, France
[6] CNRS, UMR 7213, Illkirch Graffenstaden, France
[7] DESY, European Mol Biol Lab, Hamburg Outstn, D-2000 Hamburg, Germany
[8] Inst Max Von Laue Paul Langevin, F-38042 Grenoble, France
来源
NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 05期
关键词
VITAMIN-D-RECEPTOR; SMALL-ANGLE SCATTERING; RETINOID-X-RECEPTOR; LIGAND-BINDING DOMAIN; CRYSTAL-STRUCTURE; TRANSCRIPTIONAL-ACTIVATION; STRUCTURAL DETERMINANTS; RESPONSE ELEMENT; HORMONE-RECEPTOR; NATURAL LIGAND;
D O I
10.1038/nsmb.2054
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:564 / U207
页数:8
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