Evidence map›Paper›PMID 25691471›Full record

ArticleGenes & development2015

Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis.

Maria A Schumacher, Naga Babu Chinnam, Bonnie Cuthbert, Nam K Tonthat, Travis Whitfill

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–field-weighted citation impact
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

34 citing papers in PubMed, 53 citations in OpenAlex.

  1. A c-di-AMP-controlled glutamine synthesis pathway promotes persistence ofbioRxiv : the preprint server for biology · 2026
    Article
  2. Article
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  5. Review
  6. Article
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  8. Glutamine synthetase and GlnR regulate nitrogen metabolism inApplied and environmental microbiology · 2023
    Article
  9. Review
  10. Article
  11. Alanine synthesized by alanine dehydrogenase enables ammonium-tolerant nitrogen fixation inProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Animals : an open access journal from MDPI · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. When is a transcription factor a NAP?Current opinion in microbiology · 2020
    Review
  19. Article
  20. Article
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

5 authors at 2 institutions in 1 country.

Maria A SchumacherDepartment of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA maria.schumacher@duke.edu.
Naga Babu ChinnamDepartment of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bonnie CuthbertDepartment of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nam K TonthatDepartment of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Travis WhitfillDepartment of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Duke Medical Center · USDuke University Hospital · US

Funding

MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)R01GM105404 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 2012 to 2015
$2.1M
Complete atomic dissection of the B. subtilis nitrogen regulatory pathwayR01GM115547 · NIGMS · DUKE UNIVERSITY · PI SCHUMACHER, MARIA · 2015 to 2018
$1.2M
NIGMS NIH HHS R01 GM105404NIGMS NIH HHS R01GM105404NIGMS NIH HHS R01 GM115547
6 · The paper itself

Abstract

All cells must sense and adapt to changing nutrient availability. However, detailed molecular mechanisms coordinating such regulatory pathways remain poorly understood. In Bacillus subtilis, nitrogen homeostasis is controlled by a unique circuitry composed of the regulator TnrA, which is deactivated by feedback-inhibited glutamine synthetase (GS) during nitrogen excess and stabilized by GlnK upon nitrogen depletion, and the repressor GlnR. Here we describe a complete molecular dissection of this network. TnrA and GlnR, the global nitrogen homeostatic transcription regulators, are revealed as founders of a new structural family of dimeric DNA-binding proteins with C-terminal, flexible, effector-binding sensors that modulate their dimerization. Remarkably, the TnrA sensor domains insert into GS intersubunit catalytic pores, destabilizing the TnrA dimer and causing an unprecedented GS dodecamer-to-tetradecamer conversion, which concomitantly deactivates GS. In contrast, each subunit of the GlnK trimer "templates" active TnrA dimers. Unlike TnrA, GlnR sensors mediate an autoinhibitory dimer-destabilizing interaction alleviated by GS, which acts as a GlnR chaperone. Thus, these studies unveil heretofore unseen mechanisms by which inducible sensor domains drive metabolic reprograming in the model Gram-positive bacterium B. subtilis.

Indexed as

Models, MolecularAmino Acid SequenceBacillus subtilisBacterial ProteinsCrystallizationDimerizationDNAEnzyme ActivationGlutamate-Ammonia LigaseHomeostasisNitrogenProtein Structure, TertiaryRepressor ProteinsSequence AlignmentBacterial ProteinsDNAGlutamate-Ammonia LigaseNitrogenRepressor ProteinsScgR protein, Bacillus subtilisdodecamerglutamine synthetaseMerR familytetradecamerTnrA/GlnR family

Identifiers

PMID25691471
PMCPMC4335299
OpenAlexW2104811944

What OpenQuestion holds

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Registered trials

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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.