ArticleProceedings of the National Academy of Sciences of the United States of America2015
Metalloregulator CueR biases RNA polymerase's kinetic sampling of dead-end or open complex to repress or activate transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Whole-cell biosensors with regulatory circuits based on a synthetic dual-input promoter enabling the highly sensitive detection of ultra-trace CdSynthetic and systems biotechnology · 2026Article
- Electron Paramagnetic Resonance Spectroscopy Reveals Promoter Dependent Transcription Regulation by Copper Activated CueR in Pseudomonas aeruginosa.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- Analysis of Complex Single-Molecule Kinetics: A Protocol for Single-Molecule Interaction Simulations (SMIS).Methods in molecular biology (Clifton, N.J.) · 2026Article
- A 'through-DNA' mechanism for co-regulation of metal uptake and efflux.Nature communications · 2024Article
- The Copper Efflux Regulator (CueR).Sub-cellular biochemistry · 2024Review
- Copper Efflux System Required in Murine Lung Infection by Haemophilus influenzae Composed of a Canonical ATPase Gene and Tandem Chaperone Gene Copies.Infection and immunity · 2023Article
- Probing Oxidant Effects on Superoxide Dismutase 1 Oligomeric States in Live Cells Using Single-Molecule Fluorescence Anisotropy.Chemical & biomedical imaging · 2023Article
- The protein scaffold calibrates metal specificity and activation in MerR sensors.Microbial biotechnology · 2022Article
- EPR Spectroscopy Provides New Insights into Complex Biological Reaction Mechanisms.The journal of physical chemistry. B · 2022Review
- The use of EPR spectroscopy to study transcription mechanisms.Biophysical reviews · 2022Review
- Unique underlying principles shaping copper homeostasis networks.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Review
- Allostery-driven changes in dynamics regulate the activation of bacterial copper transcription factor.Protein science : a publication of the Protein Society · 2022Article
- Cu(ii)-based DNA labeling identifies the structural link between transcriptional activation and termination in a metalloregulator.Chemical science · 2022Article
- Article
- CueR activates transcription through a DNA distortion mechanism.Nature chemical biology · 2021Article
- The bacterial multidrug resistance regulator BmrR distorts promoter DNA to activate transcription.Nature communications · 2020Article
- Dissection of Interaction Kinetics through Single-Molecule Interaction Simulation.Analytical chemistry · 2020Article
- Biphasic unbinding of a metalloregulator from DNA for transcription (de)repression in Live Bacteria.Nucleic acids research · 2020Article
- CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis inFrontiers in microbiology · 2020Article
- Unraveling the Impact of Cysteine-to-Serine Mutations on the Structural and Functional Properties of Cu(I)-Binding Proteins.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Metalloregulators respond to metal ions to regulate transcription of metal homeostasis genes. MerR-family metalloregulators act on σ(70)-dependent suboptimal promoters and operate via a unique DNA distortion mechanism in which both the apo and holo forms of the regulators bind tightly to their operator sequence, distorting DNA structure and leading to transcription repression or activation, respectively. It remains unclear how these metalloregulator-DNA interactions are coupled dynamically to RNA polymerase (RNAP) interactions with DNA for transcription regulation. Using single-molecule FRET, we study how the copper efflux regulator (CueR)--a Cu(+)-responsive MerR-family metalloregulator--modulates RNAP interactions with CueR's cognate suboptimal promoter PcopA, and how RNAP affects CueR-PcopA interactions. We find that RNAP can form two noninterconverting complexes at PcopA in the absence of nucleotides: a dead-end complex and an open complex, constituting a branched interaction pathway that is distinct from the linear pathway prevalent for transcription initiation at optimal promoters. Capitalizing on this branched pathway, CueR operates via a "biased sampling" instead of "dynamic equilibrium shifting" mechanism in regulating transcription initiation; it modulates RNAP's binding-unbinding kinetics, without allowing interconversions between the dead-end and open complexes. Instead, the apo-repressor form reinforces the dominance of the dead-end complex to repress transcription, and the holo-activator form shifts the interactions toward the open complex to activate transcription. RNAP, in turn, locks CueR binding at PcopA into its specific binding mode, likely helping amplify the differences between apo- and holo-CueR in imposing DNA structural changes. Therefore, RNAP and CueR work synergistically in regulating transcription.
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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.