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PMID: 10698945 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.

The EMBO journal ·Vol. 19 ·No. 5 ·2000-03-01 ·Pages 1045-54

Rastinejad F, Wagner T, Zhao Q, Khorasanizadeh S

Abstract

The 9-cis retinoic acid receptor (retinoid X receptor, RXR) forms heterodimers with the all-trans retinoic acid receptor (RAR) and other nuclear receptors on DNA regulatory sites composed of tandem binding elements. We describe the 1.70 A 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 RXR-RAR complex are distinct from those of the RXR homodimer, which also binds DR1. Together, these structures illustrate how the nuclear receptor superfamily exploits conformational flexibility and locally induced structures to generate combinatorial transcription factors.

MeSH Terms
Amino Acid Sequence Animals Binding Sites DNA-Binding Proteins/chemistry,genetics,metabolism Escherichia coli Molecular Sequence Data Phosphoproteins/chemistry,genetics,metabolism Protein Binding Protein Conformation Receptors, Retinoic Acid/chemistry,genetics,metabolism Retinoid X Receptors Transcription Factors/chemistry,genetics,metabolism
Chemicals
DNA-Binding Proteins Phosphoproteins Receptors, Retinoic Acid Retinoid X Receptors Transcription Factors down-regulator of transcription 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Rastinejad F
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA,.
Wagner T
Zhao Q
Khorasanizadeh S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.5.1045
Published
2000-03-01
Pages
1045-54
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305643
Subset
IM
Grants
NIGMS NIH HHS · R01 GM055217 · United States
NIGMS NIH HHS · GM55217 · United States
External Links
PubMed source DOI: 10.1093/emboj/19.5.1045 PMC Full Text View journal details
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