ArticleThe Journal of biological chemistry2015
Generating a Metal-responsive Transcriptional Regulator to Test What Confers Metal Sensing in Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- A metal-trap tests and refines blueprints to engineer cellular protein metalation with different elements.Nature communications · 2025Article
- Activation of zinc uptake regulator by zinc binding to three regulatory sites.Nucleic acids research · 2024Article
- Characterization of the Zinc Uptake Repressor (Zur) fromBiochemistry · 2024Article
- Zinc homeostasis in Pseudomonas.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Principles and practice of determining metal-protein affinities.The Biochemical journal · 2021Review
- Advances in Understanding of the Copper Homeostasis inInternational journal of molecular sciences · 2021Review
- The requirement for cobalt in vitamin BBiochimica et biophysica acta. Molecular cell research · 2021Review
- The interplay of the metallosensor CueR with two distinct CopZ chaperones defines copper homeostasis inThe Journal of biological chemistry · 2019Article
- Bacterial sensors define intracellular free energies for correct enzyme metalation.Nature chemical biology · 2019Article
- Essential trace elemental levels (zinc, iron and copper) in the biological samples of smoker referent and pulmonary tuberculosis patients.Toxicology reports · 2019Article
- Bacterial zinc uptake regulator proteins and their regulons.Biochemical Society transactions · 2018Review
- Fine control of metal concentrations is necessary for cells to discern zinc from cobalt.Nature communications · 2017Article
- Sort-Seq Approach to Engineering a Formaldehyde-Inducible Promoter for Dynamically Regulated Escherichia coli Growth on Methanol.ACS synthetic biology · 2017Article
- Metallochaperones and metalloregulation in bacteria.Essays in biochemistry · 2017Review
- A tight tunable range for Ni(II) sensing and buffering in cells.Nature chemical biology · 2017Article
- Essential and toxic metals in serum of individuals with active pulmonary tuberculosis in an endemic region.Journal of clinical tuberculosis and other mycobacterial diseases · 2017Article
- The mechanism of a formaldehyde-sensing transcriptional regulator.Scientific reports · 2016Article
- Bacterial Strategies to Maintain Zinc Metallostasis at the Host-Pathogen Interface.The Journal of biological chemistry · 2016Review
- The Effectors and Sensory Sites of Formaldehyde-responsive Regulator FrmR and Metal-sensing Variant.The Journal of biological chemistry · 2016Article
- Formaldehyde Stress Responses in Bacterial Pathogens.Frontiers in microbiology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
FrmR from Salmonella enterica serovar typhimurium (a CsoR/RcnR-like transcriptional de-repressor) is shown to repress the frmRA operator-promoter, and repression is alleviated by formaldehyde but not manganese, iron, cobalt, nickel, copper, or Zn(II) within cells. In contrast, repression by a mutant FrmRE64H (which gains an RcnR metal ligand) is alleviated by cobalt and Zn(II). Unexpectedly, FrmR was found to already bind Co(II), Zn(II), and Cu(I), and moreover metals, as well as formaldehyde, trigger an allosteric response that weakens DNA affinity. However, the sensory metal sites of the cells' endogenous metal sensors (RcnR, ZntR, Zur, and CueR) are all tighter than FrmR for their cognate metals. Furthermore, the endogenous metal sensors are shown to out-compete FrmR. The metal-sensing FrmRE64H mutant has tighter metal affinities than FrmR by approximately 1 order of magnitude. Gain of cobalt sensing by FrmRE64H remains enigmatic because the cobalt affinity of FrmRE64H is substantially weaker than that of the endogenous cobalt sensor. Cobalt sensing requires glutathione, which may assist cobalt access, conferring a kinetic advantage. For Zn(II), the metal affinity of FrmRE64H approaches the metal affinities of cognate Zn(II) sensors. Counter-intuitively, the allosteric coupling free energy for Zn(II) is smaller in metal-sensing FrmRE64H compared with nonsensing FrmR. By determining the copies of FrmR and FrmRE64H tetramers per cell, then estimating promoter occupancy as a function of intracellular Zn(II) concentration, we show how a modest tightening of Zn(II) affinity, plus weakened DNA affinity of the apoprotein, conspires to make the relative properties of FrmRE64H (compared with ZntR and Zur) sufficient to sense Zn(II) inside cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.