Evidence map›Paper›PMID 38538913›Full record

ArticleNature structural & molecular biology2024

Molecular stripping underpins derepression of a toxin-antitoxin system.

Grzegorz J Grabe, Rachel T Giorgio, Miłosz Wieczór, Bridget Gollan, Molly Sargen, Modesto Orozco, Stephen A Hare, Sophie Helaine

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
5.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Grzegorz J GrabeDepartment of Microbiology, Harvard Medical School, Boston, MA, USA. grzegorz_grabe@hms.harvard.edu.ORCID http://orcid.org/0000-0002-0419-491X
Rachel T GiorgioDepartment of Microbiology, Harvard Medical School, Boston, MA, USA.
Miłosz WieczórInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0003-4990-8629
Bridget GollanDepartment of Microbiology, Harvard Medical School, Boston, MA, USA.
Molly SargenDepartment of Microbiology, Harvard Medical School, Boston, MA, USA.
Modesto OrozcoInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0002-8608-3278
Stephen A HareSchool of Life Sciences, University of Sussex, Brighton, UK.
Sophie HelaineDepartment of Microbiology, Harvard Medical School, Boston, MA, USA. sophie_helaine@hms.harvard.edu.ORCID http://orcid.org/0000-0002-9877-4180
Harvard University · USInstitute for Research in Biomedicine · ESUniversity of Sussex · GB

Funding

The physiological activation and consequences of Toxin-Antitoxin systems in SalmonellaR01AI155552 · NIAID · HARVARD MEDICAL SCHOOL · PI HELAINE, SOPHIE · 2021 to 2025
$2.5M
NIAID NIH HHS R01 AI155552
6 · The paper itself

Abstract

Transcription factors control gene expression; among these, transcriptional repressors must liberate the promoter for derepression to occur. Toxin-antitoxin (TA) modules are bacterial elements that autoregulate their transcription by binding the promoter in a T:A ratio-dependent manner, known as conditional cooperativity. The molecular basis of how excess toxin triggers derepression has remained elusive, largely because monitoring the rearrangement of promoter-repressor complexes, which underpin derepression, is challenging. Here, we dissect the autoregulation of the Salmonella enterica tacAT3 module. Using a combination of assays targeting DNA binding and promoter activity, as well as structural characterization, we determine the essential TA and DNA elements required to control transcription, and we reconstitute a repression-to-derepression path. We demonstrate that excess toxin triggers molecular stripping of the repressor complex off the DNA through multiple allosteric changes causing DNA distortion and ultimately leading to derepression. Thus, our work provides important insight into the mechanisms underlying conditional cooperativity.

Indexed as

Gene Expression Regulation, BacterialPromoter Regions, GeneticToxin-Antitoxin SystemsBacterial ProteinsBacterial ToxinsCrystallography, X-RayDNA, BacterialModels, MolecularProtein BindingRepressor ProteinsSalmonella entericaTranscription, GeneticBacterial ProteinsBacterial ToxinsDNA, BacterialRepressor Proteins

Identifiers

PMID38538913
PMCPMC11999232
OpenAlexW4393225304

What OpenQuestion holds

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Registered trials

None linked

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.