Evidence map›Paper›PMID 29965962›Full record

ArticlePLoS computational biology2018

A dual regulation mechanism of histidine kinase CheA identified by combining network-dynamics modeling and system-level input-output data.

Bernardo A Mello, Wenlin Pan, Gerald L Hazelbauer, Yuhai Tu

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. The structural logic of dynamic signaling in the Escherichia coli serine chemoreceptor.Protein science : a publication of the Protein Society · 2024
    Article
  3. Article
  4. The Structural Logic of Dynamic Signaling in thebioRxiv : the preprint server for biology · 2024
    Article
  5. Signal integration in chemoreceptor complexes.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Structural conditions on complex networks for the Michaelis-Menten input-output response.Proceedings of the National Academy of Sciences of the United States of America · 2018
    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

4 authors at 3 institutions in 2 countries.

Bernardo A MelloIBM T. J. Watson Research Center, Yorktown Heights, New York, United States of America.ORCID 0000-0002-9261-8013
Wenlin PanDepartment of Biochemistry, University of Missouri, Columbia, Missouri, United States of America.
Gerald L HazelbauerDepartment of Biochemistry, University of Missouri, Columbia, Missouri, United States of America.
Yuhai TuIBM T. J. Watson Research Center, Yorktown Heights, New York, United States of America.
University of Missouri · USIBM Research - Thomas J. Watson Research Center · USUniversidade de Brasília · BR

Funding

Molecular Studies of Chemoreception: Administrative Supplement for EquipmentR37GM029963 · NIGMS · UNIVERSITY OF MISSOURI-COLUMBIA · PI HAZELBAUER, GERALD L. · 2012 to 2021
$5.7M
MOLECULAR STUDIES OF CHEMORECEPTIONR01GM029963 · NIGMS · WASHINGTON STATE UNIVERSITY · PI HAZELBAUER, GERALD L. · 1985 to 2010
$4.2M
Quantitative Modeling of Signal Transduction in Bacterial ChemotaxisR01GM081747 · NIGMS · IBM THOMAS J. WATSON RESEARCH CENTER · PI TU, YUHAI · 2007 to 2018
$2.6M
NIGMS NIH HHS R01 GM029963NIGMS NIH HHS R01 GM081747NIGMS NIH HHS R37 GM029963
6 · The paper itself

Abstract

It is challenging to decipher molecular mechanisms in biological systems from system-level input-output data, especially for complex processes that involve interactions among multiple components. We addressed this general problem for the bacterial histidine kinase CheA, the activity of which is regulated in chemotaxis signaling complexes by bacterial chemoreceptors. We developed a general network model to describe the dynamics of the system, treating the receptor complex with coupling protein CheW and the P3P4P5 domains of kinase CheA as a regulated enzyme with two substrates, ATP and P1, the phosphoryl-accepting domain of CheA. Our simple network model allowed us to search hypothesis space systematically. For different and progressively more complex regulation schemes, we fit our models to a large set of input-output data with the aim of identifying the simplest possible regulation mechanisms consistent with the data. Our modeling and analysis revealed novel dual regulation mechanisms in which receptor activity regulated ATP binding plus one other process, either P1 binding or phosphoryl transfer between P1 and ATP. Strikingly, in our models receptor control affected the kinetic rate constants of substrate association and dissociation equally and thus did not alter the respective equilibrium constants. We suggest experiments that could distinguish between the two dual-regulation mechanisms. This systems-biology approach of combining modeling and a large input-output dataset should be applicable for studying other complex biological processes.

Indexed as

Models, BiologicalAdenosine TriphosphateBiochemical PhenomenaChemotaxisComputer SimulationEscherichia coliEscherichia coli ProteinsHistidine KinaseKineticsMethyl-Accepting Chemotaxis ProteinsProtein BindingSignal TransductionSubstrate SpecificitySystems BiologyAdenosine TriphosphatecheA protein, E coliCheW protein, E coliEscherichia coli ProteinsHistidine KinaseMethyl-Accepting Chemotaxis Proteins

Identifiers

PMID29965962
PMCPMC6044545
OpenAlexW2810784684

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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.