1KB2

Crystal Structure of VDR DNA-binding Domain Bound to Mouse Osteopontin (SPP) Response Element

Summary for 1KB2

• Entry DOI: 10.2210/pdb1kb2/pdb
• Related: 1KB4 1KB6
• Descriptor: 5'-D(*CP*AP*CP*GP*GP*TP*TP*CP*AP*CP*GP*AP*GP*GP*TP*TP*CP*A)-3', 5'-D(*TP*GP*AP*AP*CP*CP*TP*CP*GP*TP*GP*AP*AP*CP*CP*GP*TP*G)-3', Vitamin D3 Receptor, ... (5 entities in total)
• Functional Keywords: vdr, nuclear receptor, protein-dna complex, vitamin d, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P11473
• Total number of polymer chains: 4
• Total formula weight: 37201.40

Authors

Shaffer, P.L.,Gewirth, D.T. (deposition date: 2001-11-05, release date: 2002-05-03, Last modification date: 2023-08-16)

Primary citation

Shaffer, P.L.,Gewirth, D.T.
Structural basis of VDR-DNA interactions on direct repeat response elements.
EMBO J., 21:2242-2252, 2002

PubMed 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.

PubMed: 11980721
DOI: 10.1093/emboj/21.9.2242

Experimental method

X-RAY DIFFRACTION (2.7 Å)