Evidence map›Paper›PMID 25197081›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Mixtures of opposing phosphorylations within hexamers precisely time feedback in the cyanobacterial circadian clock.

Jenny Lin, Justin Chew, Udaysankar Chockanathan, Michael J Rust

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

31 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. KidA, a multi-PAS domain protein, tunes the period of the cyanobacterial circadian oscillator.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  8. Regulation mechanisms of the dual ATPase in KaiC.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. 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 1 institution in 1 country.

Jenny LinDepartment of Biochemistry and Molecular Biology.
Justin ChewMedical Scientist Training Program, Pritzker School of Medicine.
Udaysankar ChockanathanDepartment of Chemistry, and.
Michael J RustDepartment of Molecular Genetics and Cell Biology, Department of Physics, and Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637 mrust@uchicago.edu.
University of Chicago · US

Funding

MEDICAL SCIENTIST TRAININGT32GM007281 · NIGMS · UNIVERSITY OF CHICAGO · PI CLARK, MARCUS RAMSAY · 1985 to 2022
$32.1M
Molecular And Cellular Biology Training ProgramT32GM007183 · NIGMS · UNIVERSITY OF CHICAGO · PI GLICK, BENJAMIN S, RICE, PHOEBE A · 1985 to 2021
$23.9M
Coupling between Circadian Rhythms and Metaboilsm in CyanobacteriaR01GM107369 · NIGMS · UNIVERSITY OF CHICAGO · PI RUST, MICHAEL · 2013 to 2017
$1.5M
NIGMS NIH HHS GM107369-01NIGMS NIH HHS R01 GM107369NIGMS NIH HHS T32 GM007183NIGMS NIH HHS T32-GM007183-35NIGMS NIH HHS T32 GM007281NIGMS NIH HHS T32-GM007281
6 · The paper itself

Abstract

Circadian oscillations are generated by the purified cyanobacterial clock proteins, KaiA, KaiB, and KaiC, through rhythmic interactions that depend on multisite phosphorylation of KaiC. However, the mechanisms that allow these phosphorylation reactions to robustly control the timing of oscillations over a range of protein stoichiometries are not clear. We show that when KaiC hexamers consist of a mixture of differentially phosphorylated subunits, the two phosphorylation sites have opposing effects on the ability of each hexamer to bind to the negative regulator KaiB. We likewise show that the ability of the positive regulator KaiA to act on KaiC depends on the phosphorylation state of the hexamer and that KaiA and KaiB recognize alternative allosteric states of the KaiC ring. Using mathematical models with kinetic parameters taken from experimental data, we find that antagonism of the two KaiC phosphorylation sites generates an ultrasensitive switch in negative feedback strength necessary for stable circadian oscillations over a range of component concentrations. Similar strategies based on opposing modifications may be used to support robustness in other timing systems and in cellular signaling more generally.

Indexed as

Circadian ClocksFeedback, PhysiologicalProtein MultimerizationAllosteric RegulationBacterial ProteinsCircadian RhythmCyanobacteriaModels, BiologicalPhosphorylationPhosphoserineProtein BindingProtein StabilityProtein SubunitsTime FactorsBacterial ProteinsPhosphoserineProtein Subunitsallosterycircadian rhythmsmathematical modeling

Identifiers

PMID25197081
PMCPMC4169968
OpenAlexW1991899181

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.