ArticleProceedings of the National Academy of Sciences of the United States of America2016
Oxidization without substrate unfolding triggers proteolysis of the peroxide-sensor, PerR.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Lon-dependent proteolysis in oxidative stress responses.Journal of bacteriology · 2025Review
- PerR functions as a redox-sensing transcription factor regulating metal homeostasis in the thermoacidophilic archaeon Saccharolobus islandicus REY15A.Nucleic acids research · 2025Article
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- The Transcriptomic Response of Cells of the Thermophilic BacteriumInternational journal of molecular sciences · 2024Article
- The Arsenal ofAntioxidants (Basel, Switzerland) · 2023Review
- Meddling with Metal Sensors: Fur-Family Proteins as Signaling Hubs.Journal of bacteriology · 2023Review
- Iron homeostasis inMicrobiology (Reading, England) · 2023Article
- Article
- Regulation of Bacterial Manganese Homeostasis and Usage During Stress Responses and Pathogenesis.Frontiers in molecular biosciences · 2022Review
- Ephedra sinica mitigates hepatic oxidative stress and inflammation via suppressing the TLR4/MyD88/NF-κB pathway in fipronil-treated rats.Environmental science and pollution research international · 2021Article
- HP1021 is a redox switch protein identified in Helicobacter pylori.Nucleic acids research · 2021Article
- The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis.Scientific reports · 2021Article
- Applications of Bacterial Degrons and Degraders - Toward Targeted Protein Degradation in Bacteria.Frontiers in molecular biosciences · 2021Review
- How Microbes Defend Themselves From Incoming Hydrogen Peroxide.Frontiers in immunology · 2021Review
- The Central Role of Redox-Regulated Switch Proteins in Bacteria.Frontiers in molecular biosciences · 2021Review
- Stress Can Induce Transcription of Toxin-Antitoxin Systems without Activating Toxin.Molecular cell · 2020Article
- Deletion of glutaredoxin promotes oxidative tolerance and intracellular infection inVirulence · 2019Article
- Sense and sensor ability: redox-responsive regulators in Listeria monocytogenes.Current opinion in microbiology · 2019Review
- Lon recognition of the replication initiator DnaA requires a bipartite degron.Molecular microbiology · 2019Article
- Redox Sensing by FeAntioxidants & redox signaling · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Peroxide operon regulator (PerR) is a broadly conserved hydrogen peroxide sensor in bacteria, and oxidation of PerR at its regulatory metal-binding site is considered irreversible. Here, we tested whether this oxidation specifically targets PerR for proteolysis. We find that oxidizing conditions stimulate PerR degradation in vivo, and LonA is the principal AAA+ (ATPases associated with diverse cellular activities) protease that degrades PerR. Degradation of PerR by LonA is recapitulated in vitro, and biochemical dissection of this degradation reveals that the presence of regulatory metal and PerR-binding DNA dramatically extends the half-life of the protein. We identified a LonA-recognition site critical for oxidation-controlled PerR turnover. Key residues for LonA-interaction are exposed to solvent in PerR lacking metal, but are buried in the metal-bound form. Furthermore, one residue critical for Lon recognition is also essential for specific DNA-binding by PerR, thus explaining how both the metal and DNA ligands prevent PerR degradation. This ligand-controlled allosteric mechanism for protease recognition provides a compelling explanation for how the oxidation-induced conformational change in PerR triggers degradation. Interestingly, the critical residues recognized by LonA and exposed by oxidation do not function as a degron, because they are not sufficient to convert a nonsubstrate protein into a LonA substrate. Rather, these residues are a conformation-discriminator sequence, which must work together with other residues in PerR to evoke efficient degradation. This mechanism provides a useful example of how other proteins with only mild or localized oxidative damage can be targeted for degradation without the need for extensive oxidation-dependent protein denaturation.
Indexed as
Identifiers
What OpenQuestion holds
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.