SNAP output for PDB entry 1kb2 [SNAP web server]

PDB-id

1kb2; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription-DNA

Method

X-ray (2.7 Å)

Summary

Crystal structure of vdr DNA-binding domain bound to mouse osteopontin (spp) response element

Reference

Shaffer PL, Gewirth DT (2002): "Structural basis of VDR-DNA interactions on direct repeat response elements." EMBO J., 21, 2242-2252. doi: 10.1093/emboj/21.9.2242.

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.