Research Article | Published:

Metal mediated sterol receptor-DNA complex association and dissociation determined by electrospray ionization mass spectrometry

Nature Biotechnology volume 16, pages 262266 (1998) | Download Citation

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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 DMA-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.

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Author information

Affiliations

  1. Nephrology Research Unit, Biomedical Mass Spectrometry Facility, Mayo Clinic/Foundation, Rochester, MN 55905.

    • Timothy D. Veenstra
    • , Theodore A. Craig
    •  & Rajiv Kumar
  2. Biomedical Mass Spectrometry Facility, Department of Biochemistry and Molecular Biology, Mayo Clinic/Foundation, Rochester, MN 55905.

    • Linda M. Benson
    • , Andy J. Tomlinson
    •  & Stephen Naylor
  3. Department of Biochemistry and Molecular Biology, Mayo Clinic/Foundation, Rochester, MN 55905.

    • Linda M. Benson
    • , Andy J. Tomlinson
    • , Rajiv Kumar
    •  & Stephen Naylor
  4. Department of Pharmacology and Clinical Pharmacological Unit, Mayo Clinic/Foundation, Rochester, MN 55905.

    • Stephen Naylor

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Correspondence to Rajiv Kumar or Stephen Naylor.

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DOI

https://doi.org/10.1038/nbt0398-262

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