1KB2: Crystal Structure Of Vdr Dna-Binding Domain Bound To Mouse Osteopontin (Spp) Response Element

Citation:
Abstract
The vitamin D receptor (VDR) forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by 3 bp of spacer DNA. We describe here the crystal structures at 2.7-2.8 A resolution of the VDR DNA-binding region (DBD) in complex with response elements from three different promoters: osteopontin (SPP), canonical DR3 and osteocalcin (OC). These structures reveal the chemical basis for the increased affinity of VDR for the SPP response element, and for the poor stability of the VDR-OC complex, relative to the canonical DR3 response element. The homodimeric protein-protein interface is stabilized by van der Waals interactions and is predominantly non-polar. An extensive alpha-helix at the C-terminal end of the VDR DBD resembles that found in the thyroid hormone receptor (TR), and suggests a mechanism by which VDR and TR discriminate among response elements. Selective structure-based mutations in the asymmetric homodimeric interface result in a VDR DBD protein that is defective in homodimerization but now forms heterodimers with the 9-cis retinoic acid receptor (RXR) DBD.
PDB ID: 1KB2Download
MMDB ID: 49929
PDB Deposition Date: 2001/11/5
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1KB2: tetrameric; determined by author
Molecular Components in 1KB2
Label Count Molecule
Proteins (2 molecules)
2
Vitamin D3 Receptor(Gene symbol: VDR)
Molecule annotation
Nucleotides(2 molecules)
1
5'- D(*cp*ap*cp*gp*gp*tp*tp*cp*ap*cp*gp*ap*gp*gp*tp*tp*cp*a)- 3'
Molecule annotation
1
5'- D(*tp*gp*ap*ap*cp*cp*tp*cp*gp*tp*gp*ap*ap*cp*cp*gp*tp*g)- 3'
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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