期刊
EMBO JOURNAL
卷 19, 期 5, 页码 1045-1054出版社
OXFORD UNIV PRESS
DOI: 10.1093/emboj/19.5.1045
关键词
nuclear receptor; RAR; RXR; structure; transcription factor
资金
- NIGMS NIH HHS [R01 GM055217, GM55217] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM055217] Funding Source: NIH RePORTER
The 9-cis retinoic acid receptor (retinoid X receptor, RXR) forms heterodimers with the all-ti ails retinoic acid receptor (RAR) and other nuclear receptors on DNA regulatory sites composed of tandem binding elements. We describe the 1.70 Angstrom resolution structure of the ternary complex of RXR and RAR DNA-binding regions in complex with the retinoic acid response element DR1. The receptors recognize identical half-sites through extensive base-specific contacts; however, RXR binds exclusively to the 3' site to form an asymmetric complex with the reverse polarity of other RXR heterodimers, The subunits associate in a strictly DNA-dependent manner using the T-box of RXR and the Zn-II region of RAR, both of which are reshaped in forming the complex, The protein-DNA contacts, the dimerization interface and the DNA curvature in the RSR-RAR complex are distinct from those of the RXR homodimer, which also binds DR1, Together, these structures illustrate ho vv the nuclear receptor superfamily exploits conformational flexibility and locally induced structures to generate combinatorial transcription factors.
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