PDB 1KB2 deposited: 2001-11-05 modified: 2009-02-24
Title Crystal Structure of VDR DNA-binding Domain Bound to Mouse Osteopontin (SPP) Response Element
Authors Gewirth, D.T., Shaffer, P.L.
Structure factors resolution 2.7 rfactor 0.226 rfree 0.289
DPI 1.11 theoretical min: 0.49
Related PDB Entries 1KB4 1KB6

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.

EMBO J. 2002 May; 21(9):2242-2252 doi:10.1093/emboj/21.9.2242

Cross References
Database source Identifier Description
PubMed 11980721 EMJODG
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1KB2/1 1KB2 1 tetramer 0 4 4 2080