Evidence map›Paper›PMID 23207918›Full record

ArticleGenes & development2012

Direct interactions between the coiled-coil tip of DksA and the trigger loop of RNA polymerase mediate transcriptional regulation.

Christopher W Lennon, Wilma Ross, Stephen Martin-Tumasz, Innokenti Toulokhonov, Catherine E Vrentas, Steven T Rutherford, Jeong-Hyun Lee, Samuel E Butcher, Richard L Gourse

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing 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

56 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
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  6. Review
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  11. TheMicroorganisms · 2020
    Article
  12. eLife · 2019
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Transcriptional Responses to ppGpp and DksA.Annual review of microbiology · 2018
    Review
  18. 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

9 authors at 1 institution in 1 country.

Christopher W LennonDepartment of Bacteriology, University of Wisconsin at Madison, Madison, WI 53706, USA.
Wilma Ross
Stephen Martin-Tumasz
Innokenti Toulokhonov
Catherine E Vrentas
Steven T Rutherford
Jeong-Hyun Lee
Samuel E Butcher
Richard L Gourse
University of Wisconsin–Madison · US

Funding

GRADUATE TRAINING IN MOLECULAR BIOSCIENCEST32GM007215 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HULL, CHRISTINA M · 1985 to 2018
$22.5M
WATER DISTRIB:PHYSICAL PROPERT:PIZZA &LMPS MOZZARELLA CHEESES:EARLY STAGE MATURP41RR002301 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 1985 to 2011
$13.0M
Mechanism, Activation, and Control of rRNA TranscriptionR37GM037048 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GOURSE, RICHARD L. · 2007 to 2016
$6.6M
900 MHz NMR Spectrometer Biomolecular InvestigationsP41GM066326 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN L · 2002 to 2006
$5.0M
NCRR NIH HHS P41 RR002301NCRR NIH HHS P41RR02301NIGMS NIH HHS P41 GM066326NIGMS NIH HHS P41GM66326NIGMS NIH HHS R37 GM037048NIGMS NIH HHS R37 GM37048NIGMS NIH HHS T32 GM007215
6 · The paper itself

Abstract

Escherichia coli DksA is a transcription factor that binds to RNA polymerase (RNAP) without binding to DNA, destabilizing RNAP-promoter interactions, sensitizing RNAP to the global regulator ppGpp, and regulating transcription of several hundred target genes, including those encoding rRNA. Previously, we described promoter sequences and kinetic properties that account for DksA's promoter specificity, but how DksA exerts its effects on RNAP has remained unclear. To better understand DksA's mechanism of action, we incorporated benzoyl-phenylalanine at specific positions in DksA and mapped its cross-links to RNAP, constraining computational docking of the two proteins. The resulting evidence-based model of the DksA-RNAP complex as well as additional genetic and biochemical approaches confirmed that DksA binds to the RNAP secondary channel, defined the orientation of DksA in the channel, and predicted a network of DksA interactions with RNAP that includes the rim helices and the mobile trigger loop (TL) domain. Engineered cysteine substitutions in the TL and DksA coiled-coil tip generated a disulfide bond between them, and the interacting residues were absolutely required for DksA function. We suggest that DksA traps the TL in a conformation that destabilizes promoter complexes, an interaction explaining the requirement for the DksA tip and its effects on transcription.

Indexed as

Gene Expression Regulation, BacterialDNA-Directed RNA PolymerasesEscherichia coliEscherichia coli ProteinsModels, MolecularPhenylalaninePromoter Regions, GeneticProtein BindingProtein Structure, TertiaryProtein SubunitsbenzoylphenylalaninedksA protein, E coliDNA-Directed RNA PolymerasesEscherichia coli ProteinsPhenylalanineProtein Subunits

Identifiers

PMID23207918
PMCPMC3521624
OpenAlexW2125809659

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.