Evidence map›Paper›PMID 26712005›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa.

Bruno Y Matsuyama, Petya V Krasteva, Claudine Baraquet, Caroline S Harwood, Holger Sondermann, Marcos V A S Navarro

Open access · bronzeAbstract read
In one paragraph

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 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

104 citing papers in PubMed, 166 citations in OpenAlex.

  1. Article
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  7. Multi-omics characterization of β-myrcene-evolvedFrontiers in molecular biosciences · 2026
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  9. Review
  10. ComFB, a widespread family of c-di-NMP receptor proteins.Proceedings of the National Academy of Sciences of the United States of America · 2025
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44 more citing papers are in PubMed but not listed here.

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

6 authors at 4 institutions in 3 countries.

Bruno Y MatsuyamaDepartamento de Física e Ciência Interdisciplinar, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13563-120, SP, Brazil;
Petya V KrastevaDepartment of Structural Biology and Chemistry, Unité G5 Biologie Structurale de la Sécrétion Bactérienne and UMR 3528, CNRS, Institut Pasteur, 75015 Paris, France; Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853;
Claudine BaraquetDepartment of Microbiology, University of Washington, Seattle, WA 98195.
Caroline S HarwoodDepartment of Microbiology, University of Washington, Seattle, WA 98195 csh5@uw.edu hs293@cornell.edu mvasnavarro@ifsc.usp.br.
Holger SondermannDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; csh5@uw.edu hs293@cornell.edu mvasnavarro@ifsc.usp.br.
Marcos V A S NavarroDepartamento de Física e Ciência Interdisciplinar, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13563-120, SP, Brazil; csh5@uw.edu hs293@cornell.edu mvasnavarro@ifsc.usp.br.
Universidade de São Paulo · BRUniversity of Washington · USCornell University · USInstitut Pasteur · FR

Funding

Overall (pp. 40-62)P41GM103485 · NIGMS · CORNELL UNIVERSITY · PI CERIONE, RICHARD A. · 2012 to 2018
$15.5M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Pseudomonas aeruginosa sensing and responseR01GM056665 · NIGMS · UNIVERSITY OF WASHINGTON · PI HARWOOD, CAROLINE STONE · 1998 to 2011
$3.0M
Molecular mechanism regulating periplasmic proteolysis in bacterial pathogenesisR01AI097307 · NIAID · CORNELL UNIVERSITY · PI O'TOOLE, GEORGE A., SONDERMANN, HOLGER · 2012 to 2016
$1.9M
NIAID NIH HHS R01 AI097307NIAID NIH HHS R01-AI097307NIGMS NIH HHS GM-103485NIGMS NIH HHS P41 GM103403NIGMS NIH HHS P41-GM103403NIGMS NIH HHS P41 GM103485NIGMS NIH HHS R01 GM056665NIGMS NIH HHS R01-GM56665
6 · The paper itself

Abstract

Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ(54)-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ's AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP-complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.

Indexed as

Amino Acid MotifsAmino Acid SequenceBacterial ProteinsBase SequenceBinding SitesBiofilmsCalorimetryConserved SequenceCross-Linking ReagentsCrystallography, X-RayCyclic GMPDNA, BacterialGene Expression Regulation, BacterialModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedBacterial Proteinsbis(3',5')-cyclic diguanylic acidCross-Linking ReagentsCyclic GMPDNA, BacterialFleQ protein, Pseudomonas aeruginosaMutant ProteinsSolutionsTrans-Activatorsenhancer binding proteinflagellagene expressionstructure

Identifiers

PMID26712005
PMCPMC4720306
OpenAlexW2221987900

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.