Evidence map›Paper›PMID 34233195›Full record

ArticleCell reports2021

Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone.

Mohinder Pal, Hugo Muñoz-Hernandez, Dennis Bjorklund, Lihong Zhou, Gianluca Degliesposti, J Mark Skehel, Emma L Hesketh, Rebecca F Thompson, Laurence H Pearl, Oscar Llorca and 1 more

Abstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Review
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  9. Differential roles of putative arginine fingers of AAAbioRxiv : the preprint server for biology · 2024
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  12. Review
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  14. A virus-induced circular RNA maintains latent infection of Kaposi's sarcoma herpesvirus.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Review
  16. Article
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  20. Review
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

11 authors.

Mohinder PalGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Hugo Muñoz-HernandezSpanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Dennis BjorklundGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Lihong ZhouGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Gianluca DegliespostiMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
J Mark SkehelMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Emma L HeskethAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Rebecca F ThompsonAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Laurence H PearlGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK; Division of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW1E 6BT, UK. Electronic address: laurence.pearl@sussex.ac.uk.
Oscar LlorcaSpanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: ollorca@cnio.es.
Chrisostomos ProdromouGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.

Funding

Biotechnology and Biological Sciences Research Council BB/R01678X/1Medical Research Council MC_U105184326Wellcome TrustWellcome Trust 095605/Z/11/AWellcome Trust 095605/Z/11/ZWellcome Trust 108466/Z/15/Z
6 · The paper itself

Abstract

The R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) complex, in collaboration with heat shock protein 90 (HSP90), functions as a chaperone for the assembly and stability of protein complexes, including RNA polymerases, small nuclear ribonucleoprotein particles (snRNPs), and phosphatidylinositol 3-kinase (PI3K)-like kinases (PIKKs) such as TOR and SMG1. PIKK stabilization depends on an additional complex of TELO2, TTI1, and TTI2 (TTT), whose structure and function are poorly understood. The cryoelectron microscopy (cryo-EM) structure of the human R2TP-TTT complex, together with biochemical experiments, reveals the mechanism of TOR recruitment to the R2TP-TTT chaperone. The HEAT-repeat TTT complex binds the kinase domain of TOR, without blocking its activity, and delivers TOR to the R2TP chaperone. In addition, TTT regulates the R2TP chaperone by inhibiting RUVBL1-RUVBL2 ATPase activity and by modulating the conformation and interactions of the PIH1D1 and RPAP3 components of R2TP. Taken together, our results show how TTT couples the recruitment of TOR to R2TP with the regulation of this chaperone system.

Indexed as

Adenosine TriphosphatasesCryoelectron MicroscopyHumansModels, MolecularMolecular ChaperonesMultiprotein ComplexesProtein BindingProtein DomainsProtein Interaction MappingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStructure-Activity RelationshipAdenosine TriphosphatasesMolecular ChaperonesMultiprotein ComplexesSaccharomyces cerevisiae ProteinsHSP90 chaperonemTORPIKKR2TPRUVBL1RUVBL2TELO2TTI1TTI2TTT

Identifiers

PMID34233195
PMCPMC8278493

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.