Evidence map›Paper›PMID 30254053›Full record

ArticleScience signaling2018

Substrate binding allosterically relieves autoinhibition of the pseudokinase TRIB1.

Sam A Jamieson, Zheng Ruan, Abigail E Burgess, Jack R Curry, Hamish D McMillan, Jodi L Brewster, Anita K Dunbier, Alison D Axtman, Natarajan Kannan, Peter D Mace

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 61 citations in OpenAlex.

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  13. Emerging functions of pseudoenzymes.The Biochemical journal · 2023
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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

10 authors at 3 institutions in 2 countries.

Sam A JamiesonBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.ORCID 0000-0003-0120-4737
Zheng RuanInstitute of Bioinformatics, University of Georgia, Athens, GA 30602, USA.ORCID 0000-0002-4412-4916
Abigail E BurgessBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.ORCID 0000-0002-3522-6347
Jack R CurryBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.ORCID 0000-0001-8829-9913
Hamish D McMillanBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.ORCID 0000-0002-1384-8567
Jodi L BrewsterBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.ORCID 0000-0001-8569-1813
Anita K DunbierBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.ORCID 0000-0003-4621-7419
Alison D AxtmanStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0003-4779-9932
Natarajan KannanInstitute of Bioinformatics, University of Georgia, Athens, GA 30602, USA.
Peter D MaceBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand. peter.mace@otago.ac.nz.ORCID 0000-0003-2175-9537
University of Otago · NZUniversity of Georgia · USUniversity of North Carolina at Chapel Hill · US

Funding

Functional Annotation of Natural and Disease Variants in Tryosine KinasesR01GM114409 · NIGMS · UNIVERSITY OF GEORGIA · PI KANNAN, NATARAJAN · 2015 to 2020
$1.6M
NIGMS NIH HHS R01 GM114409Wellcome TrustWellcome Trust 106169/ZZ14/Z
6 · The paper itself

Abstract

The Tribbles family of pseudokinases recruits substrates to the ubiquitin ligase COP1 to facilitate ubiquitylation. CCAAT/enhancer-binding protein (C/EBP) family transcription factors are crucial Tribbles substrates in adipocyte and myeloid cell development. We found that the TRIB1 pseudokinase was able to recruit various C/EBP family members and that the binding of C/EBPβ was attenuated by phosphorylation. To explain the mechanism of C/EBP recruitment, we solved the crystal structure of TRIB1 in complex with C/EBPα, which revealed that TRIB1 underwent a substantial conformational change relative to its substrate-free structure and bound C/EBPα in a pseudosubstrate-like manner. Crystallographic analysis and molecular dynamics and subsequent biochemical assays showed that C/EBP binding triggered allosteric changes that link substrate recruitment to COP1 binding. These findings offer a view of pseudokinase regulation with striking parallels to bona fide kinase regulation-by means of the activation loop and αC helix-and raise the possibility of small molecules targeting either the activation "loop-in" or "loop-out" conformations of Tribbles pseudokinases.

Indexed as

Allosteric SiteCCAAT-Enhancer-Binding ProteinsCrystallography, X-RayFluorometryHumansIntracellular Signaling Peptides and ProteinsMolecular Dynamics SimulationPhosphorylationProtein BindingProtein DomainsProtein Serine-Threonine KinasesSubstrate SpecificityUbiquitin-Protein LigasesCCAAT-Enhancer-Binding ProteinsCOP1 protein, humanIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesTRIB1 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID30254053
PMCPMC6553639
OpenAlexW2894214056

What OpenQuestion holds

Textmetadata
LicenceTDM
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.