Ultrasensitivity and heavy-metal selectivity of the allosterically modulated MerR transcription complex

Diana M. Ralston, Thomas V. O'Halloran*

*Corresponding author for this work

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

The MerR metalloregulatory protein is a heavy-metal receptor that functions as the represser and Hg(II)-responsive transcription activator of the prokaryotic mercury-resistance (mer) genes. We demonstrate that this allosterically modulated regulatory protein is sensitive to HgCl2 concentrations of 1.0 ± 0.3 × 10-8 M in the presence of 1.0 × 10-3 M dithiothreitol for half-maximal induction of transcription of the mer promoter by Escherichia coli RNA polymerase in vitro. Transcription mediated by MerR increases from 10% to 90% of maximum in response to a 7-fold change in concentration of HgCl2, consistent with a threshold phenomenon known as ultrasensitivity. In addition, MerR exhibits a high degree of selectivity. Cd(II), Zn(II), Ag(I), Au(I), and Au(III) have been found to partially stimulate transcription in the presence of MerR, but concentrations at least two to three orders of magnitude greater than for Hg(II) are required. The molecular basis of the ultrasensitivity and selectivity phenomena are postulated to arise from the unusual topology of the transcription complex and a rare trigonal mercuric ion coordination environment, respectively. This mercuric ion-induced switch is to our knowledge the only known example of ultrasensitivity in a signal-responsive transcription mechanism.

Original languageEnglish (US)
Pages (from-to)3846-3850
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number10
DOIs
StatePublished - 1990

Keywords

  • Mercuric thiolate chemistry
  • Mercury resistance
  • Metalloregulatory protein
  • Transcriptional activation

ASJC Scopus subject areas

  • General

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