Evidence map›Paper›PMID 27219477›Full record

ArticlePLoS biology2016

Structure, Regulation, and Inhibition of the Quorum-Sensing Signal Integrator LuxO.

Hande Boyaci, Tayyab Shah, Amanda Hurley, Bashkim Kokona, Zhijie Li, Christian Ventocilla, Philip D Jeffrey, Martin F Semmelhack, Robert Fairman, Bonnie L Bassler and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

29 citing papers in PubMed, 41 citations in OpenAlex.

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  11. CombinedACS omega · 2023
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  13. Natural Silencing of Quorum-Sensing Activity ProtectsbioRxiv : the preprint server for biology · 2023
    Article
  14. Article
  15. Article
  16. Small regulatory RNAs inmicroLife · 2023
    Review
  17. Article
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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

11 authors at 3 institutions in 1 country.

Hande BoyaciDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Tayyab ShahDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.ORCID 0000-0002-1548-2888
Amanda HurleyDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Bashkim KokonaDepartment of Biology, Haverford College, Haverford, Pennsylvania, United States of America.ORCID 0000-0003-4264-8940
Zhijie LiDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Christian VentocillaDepartment of Chemistry, Princeton University, Princeton, New Jersey, United States of America.
Philip D JeffreyDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Martin F SemmelhackDepartment of Chemistry, Princeton University, Princeton, New Jersey, United States of America.
Robert FairmanDepartment of Biology, Haverford College, Haverford, Pennsylvania, United States of America.
Bonnie L BasslerDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Frederick M HughsonDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Princeton University · USHaverford College · USHoward Hughes Medical Institute · US

Funding

Life Science and Biomedical technology Research center at NSLS-II LSBRP41GM111244 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI MCSWEENEY, SEAN · 2014 to 2018
$16.4M
Overall (pp. 40-62)P41GM103485 · NIGMS · CORNELL UNIVERSITY · PI CERIONE, RICHARD A. · 2012 to 2018
$15.5M
Case Center for Synchrotron BiosciencesP30EB009998 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2009 to 2018
$8.4M
Structure-Function Analysis of AI-2 Quorum SensingR01AI054442 · NIAID · PRINCETON UNIVERSITY · PI HUGHSON, FREDERICK M · 2003 to 2012
$4.5M
Intra-and Inter-Species Communication in BacteriaR01GM065859 · NIGMS · PRINCETON UNIVERSITY · PI BASSLER, BONNIE L · 2002 to 2015
$4.2M
Intra- and Inter- Species Communication in BacteriaR37GM065859 · NIGMS · PRINCETON UNIVERSITY · PI BASSLER, BONNIE L · 2016 to 2025
$3.4M
Manipulating Quorum Sensing to Control Bacterial PathogenicityR56AI091681 · NIAID · PRINCETON UNIVERSITY · PI HUGHSON, FREDERICK M · 2012 to 2012
$398k
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI054442NIAID NIH HHS R56 AI091681NIBIB NIH HHS P30 EB009998NIGMS NIH HHS P41 GM103485NIGMS NIH HHS P41 GM111244NIGMS NIH HHS R01 GM065859NIGMS NIH HHS R37 GM065859
6 · The paper itself

Abstract

In a process called quorum sensing, bacteria communicate with chemical signal molecules called autoinducers to control collective behaviors. In pathogenic vibrios, including Vibrio cholerae, the accumulation of autoinducers triggers repression of genes responsible for virulence factor production and biofilm formation. The vibrio autoinducer molecules bind to transmembrane receptors of the two-component histidine sensor kinase family. Autoinducer binding inactivates the receptors' kinase activities, leading to dephosphorylation and inhibition of the downstream response regulator LuxO. Here, we report the X-ray structure of LuxO in its unphosphorylated, autoinhibited state. Our structure reveals that LuxO, a bacterial enhancer-binding protein of the AAA+ ATPase superfamily, is inhibited by an unprecedented mechanism in which a linker that connects the catalytic and regulatory receiver domains occupies the ATPase active site. The conformational change that accompanies receiver domain phosphorylation likely disrupts this interaction, providing a mechanistic rationale for LuxO activation. We also determined the crystal structure of the LuxO catalytic domain bound to a broad-spectrum inhibitor. The inhibitor binds in the ATPase active site and recapitulates elements of the natural regulatory mechanism. Remarkably, a single inhibitor molecule may be capable of inhibiting an entire LuxO oligomer.

Indexed as

Bacterial ProteinsBinding SitesCrystallography, X-RayModels, MolecularPhosphorylationProtein DomainsRepressor ProteinsUracilazauracilBacterial ProteinsRepressor ProteinsUracil

Identifiers

PMID27219477
PMCPMC4878744
OpenAlexW2344843461

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.