Evidence map›Paper›PMID 25087511›Full record

ArticleStructure (London, England : 1993)2014

Cys-scanning disulfide crosslinking and bayesian modeling probe the transmembrane signaling mechanism of the histidine kinase, PhoQ.

Kathleen S Molnar, Massimiliano Bonomi, Riccardo Pellarin, Graham D Clinthorne, Gabriel Gonzalez, Shalom D Goldberg, Mark Goulian, Andrej Sali, William F DeGrado

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

69 citing papers in PubMed, 121 citations in OpenAlex.

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  6. A Model of the Full-Length Cytokinin Receptor: New Insights and Prospects.International journal of molecular sciences · 2023
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  7. The inhibitory mechanism of a small protein reveals its role in antimicrobial peptide sensing.Proceedings of the National Academy of Sciences of the United States of America · 2023
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  13. Review
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  16. Review
  17. Characterization of an A3G-VifMolecular & cellular proteomics : MCP · 2021
    Article
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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Kathleen S MolnarDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group19104, USA, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Massimiliano BonomiDepartment of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Riccardo PellarinDepartment of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Graham D ClinthornePharmacological Sciences Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gabriel GonzalezBiochemistry and Molecular Biophysics Graduate Group19104, USA, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Shalom D GoldbergDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mark GoulianDepartment of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Andrej SaliDepartment of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
William F DeGradoDepartment of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: william.degrado@ucsf.edu.
University of California, San Francisco · USUniversity of Pennsylvania · US

Funding

VIRAL DEGENERATIVE DEMENTING DISEASE IN AGING (SUPP)P01AG002132 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 1985 to 2024
$51.7M
NEW TOOLS FOR EXPLORING THE DYNAMIC INTERACTOME(RMI)U54RR022220 · NCRR · ROCKEFELLER UNIVERSITY · PI ROUT, MICHAEL P · 2005 to 2011
$19.3M
TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular NeighborhoodsP41GM109824 · NIGMS · ROCKEFELLER UNIVERSITY · PI ROUT, MICHAEL P · 2014 to 2023
$18.8M
SPECIALIZED CENTER FOR THE PROTEIN STRUCTURE INITIATIVEU54GM074929 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOE, SENYON · 2005 to 2009
$16.6M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008275 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WAND, A. JOSHUA · 1988 to 2018
$6.0M
IMP: Software for Hybrid Determination of Macromolecular Assembly StructuresR01GM083960 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 2008 to 2024
$5.2M
Regulation of Bacterial Two-Component Signaling by Small Membrane ProteinsR01GM080279 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GOULIAN, MARK D · 2007 to 2020
$3.7M
De novo design of alpha-helical bundlesR37GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 2004 to 2013
$3.6M
Design and mechanistic studies of mimics of antimicrobial peptidesR01AI074866 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 2008 to 2012
$3.0M
DE NOVO DESIGN OF ALPHA HELICAL BUNDLESR01GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 1996 to 2016
$2.4M
Design and mechanistic studies of mimics of antimicrobial peptidesR56AI074866 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEGRADO, WILLIAM · 2013 to 2013
$573k
NCRR NIH HHS U54 RR022220NIAID NIH HHS AI074866NIAID NIH HHS R01 AI074866NIAID NIH HHS R56 AI074866NIA NIH HHS P01 AG002132NIGMS NIH HHS GM54616NIGMS NIH HHS P41 GM109824NIGMS NIH HHS R01 GM054616NIGMS NIH HHS R01 GM080279NIGMS NIH HHS R01 GM083960NIGMS NIH HHS R37 GM054616NIGMS NIH HHS T32 GM008275NIGMS NIH HHS U54 GM074929
6 · The paper itself

Abstract

Bacteria transduce signals across the membrane using two-component systems (TCSs), consisting of a membrane-spanning sensor histidine kinase and a cytoplasmic response regulator. In gram-negative bacteria, the PhoPQ TCS senses cations and antimicrobial peptides, yet little is known about the structural changes involved in transmembrane signaling. We construct a model of PhoQ signal transduction using Bayesian inference, based on disulfide crosslinking data and homologous crystal structures. The data are incompatible with a single conformation but are instead consistent with two interconverting structures. These states differ in membrane depth of the periplasmic acidic patch and the reciprocal displacement of diagonal helices along the dimer interface. Studies of multiple histidine kinases suggest this repacking might be a common mode of signal transduction in sensor His-kinase receptors. Because a similar scissors model has been ruled out in CheA-linked chemoreceptors, the evidence suggests that sensor His-kinase and CheA-linked receptors possess different signaling mechanisms.

Indexed as

Bacterial ProteinsBayes TheoremComputer SimulationCystineHistidine KinaseModels, MolecularProtein KinasesProtein Structure, SecondaryProtein Structure, TertiaryStructural Homology, ProteinBacterial ProteinsCystineHistidine KinasePhoQ protein, BacteriaProtein Kinases

Identifiers

PMID25087511
PMCPMC4322757
OpenAlexW2042118984

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.