The Ah receptor can bind ligand in the absence of receptor-associated heat-shock protein 90

Dorothy M. Phelan, William R. Brackney, Michael S. Denison

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9 Scopus citations


The Ah receptor (AhR) is a soluble ligand-dependent DNA regulatory protein that mediates many of the biological responses to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. In the absence of ligand, the cytosolic form of the AhR is found complexed with at least two molecules of hsp90, a heat shock protein of 90 kDa. In addition to its role in AhR protein folding and ability to repress the inherent nuclear localization, dimerization, and DNA binding activity of the AhR, it has been reported that hsp90 is absolutely required for maintaining the AhR in its high-affinity ligand binding conformation. The ability of high salt conditions (0.4 M KCl) to dissociate the multimeric AhR complex into its monomeric form provides us with an avenue to examine the role of hsp90 in AhR ligand binding activity. In contrast to previous reports, we demonstrate that salt-dissociated 'hsp90-free' AhR from several species still retains the ability to specifically bind ligand ([3H]TCDD). Although partial inactivation of ligand binding of salt-dissociated rat hepatic AhR was observed (to a maximum of 50% of total AhR binding), the presence of bound ligand protected against this inactivation. Little or no inactivation of the ligand binding ability of salt-dissociated guinea pig or rabbit AhR occurred. Our results not only indicate a significant species-difference in AhR ligand binding stability and/or activity, but also demonstrate that AhR ligand binding activity does not absolutely require the presence of receptor-bound hsp90.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalArchives of Biochemistry and Biophysics
Issue number1
StatePublished - May 1 1998


  • 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • Ah receptor
  • Hsp90
  • TCDD

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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