1YNW: Crystal Structure Of Vitamin D Receptor And 9-Cis Retinoic Acid Receptor Dna-Binding Domains Bound To A Dr3 Response Element

Citation:
J. Steroid Biochem. Mol. Biol. (2004) 89-90 p.215-219
Abstract
The Vitamin D receptor (VDR) is a ligand-responsive transcription factor that forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by three base pairs of spacer DNA. Binding of 1alpha,25-dihydroxyvitamin D(3) to the full-length VDR causes destabilization of the VDR homodimer and formation of a heterodimeric complex with the 9-cis retinoic acid receptor (RXR). VDR and RXR DNA-binding domains (DBDs) do not mimic this behavior, however: VDR DBD homodimers are formed exclusively, even in the presence of excess RXR DBD. Exploiting the asymmetry of the heterodimer and our knowledge of the homodimeric DBD interface, we have engineered VDR mutants that disfavor the homodimeric complex and allow for the formation of heterodimeric DBD complexes with RXR on DR3 elements. One of these complexes has been crystallized and its structure determined. However, the polarity of the proteins relative to the DNA is non-physiological due to crystal packing between symmetry-related VDR DBD protomers. This reveals a flattened energy landscape that appears to rely on elements outside of the core DBD for response element discrimination in the heterodimer.
PDB ID: 1YNWDownload
MMDB ID: 52153
PDB Deposition Date: 2005/1/25
Updated in MMDB: 2007/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1YNW: tetrameric; determined by author
Molecular Components in 1YNW
Label Count Molecule
Proteins (2 molecules)
1
Vitamin D3 Receptor(Gene symbol: VDR)
Molecule annotation
1
Retinoic Acid Receptor Rxr-alpha(Gene symbol: RXRA)
Molecule annotation
Nucleotides(2 molecules)
1
5'-d(*tp*tp*ap*gp*gp*tp*cp*ap*cp*gp*ap*ap*gp*gp*tp*cp*ap*a) -3'
Molecule annotation
1
5'-d(*tp*tp*tp*gp*ap*cp*cp*tp*tp*cp*gp*tp*gp*ap*cp*cp*tp*a) -3'
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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