1YNW

Crystal Structure of Vitamin D Receptor and 9-cis Retinoic Acid Receptor DNA-Binding Domains Bound to a DR3 Response Element

Summary for 1YNW

• Entry DOI: 10.2210/pdb1ynw/pdb
• Descriptor: 5'-d(*TP*TP*AP*GP*GP*TP*CP*AP*CP*GP*AP*AP*GP*GP*TP*CP*AP*A)-3', 5'-d(*TP*TP*TP*GP*AP*CP*CP*TP*TP*CP*GP*TP*GP*AP*CP*CP*TP*A)-3', Vitamin D3 Receptor, ... (5 entities in total)
• Functional Keywords: vdr; rxr; nuclear receptor; protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P11473 P19793
• Total number of polymer chains: 4
• Total formula weight: 35710.13

Authors

Shaffer, P.L.,Gewirth, D.T. (deposition date: 2005-01-25, release date: 2005-02-15, Last modification date: 2023-08-23)

Primary citation

Shaffer, P.L.,Gewirth, D.T.
Structural analysis of RXR-VDR interactions on DR3 DNA
J.Steroid Biochem.Mol.Biol., 89-90:215-219, 2004

PubMed 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.

PubMed: 15225774
DOI: 10.1016/j.jsbmb.2004.03.084

Experimental method

X-RAY DIFFRACTION (3 Å)