Evidence map›Paper›PMID 23256153›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems.

Guy E Townsend, Varsha Raghavan, Igor Zwir, Eduardo A Groisman

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  4. Determinants of raffinose family oligosaccharide use inbioRxiv : the preprint server for biology · 2024
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  8. Review
  9. Article
  10. Hybrid histidine kinase activation by cyclic di-GMP-mediated domain liberation.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Article
  12. Article
  13. Dietary sugar silences a colonization factor in a mammalian gut symbiont.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  14. Review
  15. Article
  16. Article
  17. Bacterial protein networks: properties and functions.Nature reviews. Microbiology · 2015
    Review
  18. Review
  19. Toward rationally redesigning bacterial two-component signaling systems using coevolutionary information.Proceedings of the National Academy of Sciences of the United States of America · 2014
    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

4 authors at 3 institutions in 1 country.

Guy E TownsendDepartment of Microbial Pathogenesis and Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06536.
Varsha Raghavan
Igor Zwir
Eduardo A Groisman
Washington University in St. Louis · USHoward Hughes Medical Institute · USYale University · US

Funding

MOLECULAR AND STRUCTURAL BASES OF POLYMYXIN RESISTANCER01AI042236 · NIAID · YALE UNIVERSITY · PI GROISMAN, EDUARDO · 1998 to 2013
$3.0M
Co-opting ancestral regulatory systems to control bacterial virulenceR56AI042236 · NIAID · YALE UNIVERSITY · PI GROISMAN, EDUARDO · 2015 to 2015
$368k
Howard Hughes Medical InstituteNIAID NIH HHS AI42236NIAID NIH HHS R01 AI042236NIAID NIH HHS R56 AI042236
6 · The paper itself

Abstract

Cellular processes require specific interactions between cognate protein partners and concomitant discrimination against noncognate partners. Signal transduction by classical two-component regulatory systems typically entails an intermolecular phosphoryl transfer between a sensor kinase (SK) and a cognate response regulator (RR). Interactions between noncognate partners are rare because SK/RR pairs coevolve unique interfaces that dictate phosphotransfer specificity. Here we report that the in vitro phosphotransfer specificity is relaxed in hybrid two-component systems (HTCSs) from the human gut symbiont Bacteroides thetaiotaomicron, which harbor both the SK and RR in a single polypeptide. In contrast, phosphotransfer specificity is retained in classical two-component regulatory systems from this organism. This relaxed specificity enabled us to rewire a HTCS successfully to transduce signals between noncognate SK/RR pairs. Despite the relaxed specificity between SK and RRs, HTCSs remained insulated from cross-talk with noncognate proteins in vivo. Our data suggest that the high local concentration of the SK and RR present in the same polypeptide maintains specificity while relaxing the constraints on coevolving unique contact interfaces.

Indexed as

Evolution, MolecularModels, MolecularAmino Acid SequenceBacteroidesBlotting, WesternEscherichia coliLikelihood FunctionsModels, GeneticPhosphorylationProtein EngineeringProtein KinasesReal-Time Polymerase Chain ReactionRepressor ProteinsSequence AlignmentSignal TransductionProtein KinasesRepressor Proteins

Identifiers

PMID23256153
PMCPMC3545799
OpenAlexW2003502846

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.