Pharmaceutical Sciences Faculty Publications

Title

Metal Mediated Sterol Receptor-DNA Complex Association and Dissociation Determined by Electrospray Ionization Mass Spectrometry

Document Type

Article

Publication Date

3-1-1998

Journal Title

Nature Biotechnology

ISSN

1087-0156

Volume

16

Issue

3

First Page

262

Last Page

266

DOI

10.1038/nbt0398-262

PubMed ID

9528006

Abstract

The vitamin D receptor (VDR) binds to specific DNA sequences termed vitamin D response elements (VDREs) thereby enhancing or repressing transcription. We have used electrospray ionization mass spectrometry to examine the interaction between the DNA-binding domain of the vitamin D receptor (VDR DBD) with a double-stranded DNA (dsDNA) sequence containing the VDRE from the mouse osteopontin gene. The VDR DBD was shown to bind to the appropriate DNA sequence only when bound to 2 moles of zinc (Zn2+) or cadmium (Cd2+) per mole of protein. Additional binding of Zn2+ or Cd2+ by the protein caused the protein to dissociate from the dsDNA. These results show that the VDR DBD/DNA metal-dependent association occurs when the receptor is occupied by 2 moles of Zn2+ per mole of protein and that further binding of Zn2+ to the protein causes dissociation of the complex.

Keywords

Binding sites, cadmium, DNA, mass spectrometry, osteopontin, receptors, calcitriol, sialoglycoproteins, zinc

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