Metal Mediated Sterol Receptor-DNA Complex Association and Dissociation Determined by Electrospray Ionization Mass Spectrometry
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.
Binding sites, cadmium, DNA, mass spectrometry, osteopontin, receptors, calcitriol, sialoglycoproteins, zinc
Veenstra, Timothy D.; Benson, Linda M.; Craig, Theodore A.; Tomlinson, Andy J.; Kumar, Rajiv; and Naylor, Stephen, "Metal Mediated Sterol Receptor-DNA Complex Association and Dissociation Determined by Electrospray Ionization Mass Spectrometry" (1998). Pharmaceutical Sciences Faculty Publications. 524.