Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA
Open Access
- 16 December 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 31 (2), 291-300
- https://doi.org/10.1038/emboj.2011.445
Abstract
Transcription regulation by steroid hormones and other metabolites is mediated by nuclear receptors (NRs) such as the vitamin D and retinoid X receptors (VDR and RXR). Here, we present the cryo electron microscopy (cryo‐EM) structure of the heterodimeric complex of the liganded human RXR and VDR bound to a consensus DNA response element forming a direct repeat (DR3). The cryo‐EM map of the 100‐kDa complex allows positioning the individual crystal structures of ligand‐ and DNA‐binding domains (LBDs and DBDs). The LBDs are arranged perpendicular to the DNA and are located asymmetrically at the DNA 5′‐end of the response element. The structure reveals that the VDR N‐terminal A/B domain is located close to the DNA. The hinges of both VDR and RXR are fully visible and hold the complex in an open conformation in which co‐regulators can bind. The asymmetric topology of the complex provides the structural basis for RXR being an adaptive partner within NR heterodimers, while the specific helical structure of VDR's hinge connects the 3′‐bound DBD with the 5′‐bound LBD and thereby serves as a conserved linker of defined length sensitive to mutational deletion. There is a [Have you seen?][1] (January 2012) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.475Keywords
This publication has 55 references indexed in Scilit:
- DNA binding alters coactivator interaction surfaces of the intact VDR–RXR complexNature Structural & Molecular Biology, 2011
- Functionality of unliganded VDR in breast cancer cells: repressive action on CYP24 basal transcriptionMolecular and Cellular Biochemistry, 2010
- Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNANature, 2008
- Structure of the ligand-binding domain of rat VDR in complex with the nonsecosteroidal vitamin D3analogue YR301Acta Crystallographica Section F Structural Biology and Crystallization Communications, 2008
- Fourier shell correlation threshold criteriaJournal of Structural Biology, 2005
- Visualization of release factor 3 on the ribosome during termination of protein synthesisNature, 2004
- EMAN: Semiautomated Software for High-Resolution Single-Particle ReconstructionsJournal of Structural Biology, 1999
- A New Generation of the IMAGIC Image Processing SystemJournal of Structural Biology, 1996
- The RXR heterodimers and orphan receptorsCell, 1995
- Sequence and Characterization of a Coactivator for the Steroid Hormone Receptor SuperfamilyScience, 1995