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Cited by 58Bacterial Genetics and BiotechnologyGene Regulatory Network AnalysisEscherichia coli research studies

Fine control of metal concentrations is necessary for cells to discern zinc from cobalt

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Osman, Deenah, Foster, Andrew W., Chen, Junjun, Svedaite, Kotryna, Steed, Jonathan W., Lurie-Luke, Elena, Huggins, Thomas G., Robinson, Nigel J.·2017·Nature Communications
DOI 10.1038/s41467-017-02085-zPMC PMC5709419
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Abstract

Bacteria possess transcription factors whose DNA-binding activity is altered upon binding to specific metals, but metal binding is not specific in vitro. Here we show that tight regulation of buffered intracellular metal concentrations is a prerequisite for metal specificity of Zur, ZntR, RcnR and FrmR in Salmonella Typhimurium. In cells, at non-inhibitory elevated concentrations, Zur and ZntR, only respond to Zn(II), RcnR to cobalt and FrmR to formaldehyde. However, in vitro all these sensors bind non-cognate metals, which alters DNA binding. We model the responses of these sensors to intracellular-buffered concentrations of Co(II) and Zn(II) based upon determined abundances, metal affinities and DNA affinities of each apo- and metalated sensor. The cognate sensors are modelled to respond at the lowest concentrations of their cognate metal, explaining specificity. However, other sensors are modelled to respond at concentrations only slightly higher, and cobalt or Zn(II) shock triggers mal-responses that match these predictions. Thus, perfect metal specificity is fine-tuned to a narrow range of buffered intracellular metal concentrations.

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  • Zur proteins sense Zn2+ sufficiency and the binding of Zn2+ is anywhere from 10- to 103-fold tighter when measured in the presence of DNA.

    “For example, Zur proteins sense Zn2+ sufficiency and the binding of Zn2+ is anywhere from 10- to 103-fold tighter when measured in the presence of DNA.25,27,28”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [28]

    In Results, “Thermodynamic data predict the responses to Zn(II),” Zur responds to zinc, supporting its role as a zinc sensor. In Results, “Co(II) affects DNA binding by Zur, FrmRE64H and ZntR,” the paper reports that zinc-bound Salmonella Zur binds DNA about 500-fold more tightly than apo-Zur and calculates coupling between zinc and DNA binding. It does not report measuring zinc-binding affinity in the presence of DNA, or establish the stated 10- to 10³-fold range across Zur proteins; the measured comparison is in the opposite binding direction. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Osman, D., Foster, A. W., Chen, J., Svedaite, K., Steed, J. W., Lurie-Luke, E., Huggins, T. G., & Robinson, N. J.
Affiliations
  • Durham University (GB)
  • Procter & Gamble (United States) (US)
Corresponding author
Robinson, Nigel J.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-12-01
Volume
8
Issue
1
Pages
1884-1884
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-02085-z
PMC
PMC5709419
OpenAlex
W2768348732
Cited by
58
References
5
Citations by year
2026: 2 · 2025: 10 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 12 · 2018: 5
FWCI
4.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Durham Research Online (Durham University) (acceptedVersion, cc-by)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Procter and Gamble
  • Durham University
  • Biotechnology and Biological Sciences Research Council (BB/L009226/1, BB/J017787/1, BB/L013711/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
metal ion specificity, zinc ion detection, Salmonella typhimurium, Zur, metal homeostasis, formaldehyde sensing
MeSH terms
Bacterial Proteins, Binding Sites, Cobalt, Formaldehyde, Repressor Proteins, Salmonella typhimurium, Zinc, Gene Expression Regulation, Bacterial

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