Evidence map›Paper›PMID 31444342›Full record

ArticleNature communications2019

Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.

Sarah V Faull, Andy M C Lau, Chloe Martens, Zainab Ahdash, Kjetil Hansen, Hugo Yebenes, Carla Schmidt, Fabienne Beuron, Nora B Cronin, Edward P Morris and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.8field-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

47 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Computational exploration of the significance ofWorld journal of clinical oncology · 2023
    Article
  20. COPS6 promotes tumor progression and reduces CD8Acta pharmacologica Sinica · 2023
    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

11 authors at 4 institutions in 3 countries.

Sarah V FaullDivision of Structural Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Andy M C LauDepartment of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.ORCID http://orcid.org/0000-0003-0572-7826
Chloe MartensDepartment of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.
Zainab AhdashDepartment of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.
Kjetil HansenDepartment of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.ORCID http://orcid.org/0000-0002-0085-8440
Hugo YebenesDivision of Structural Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Carla SchmidtInterdisciplinary Research Center HALOmem, Charles Tanford Protein Centre, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Strasse 3a, 06120, Halle/Saale, Germany.
Fabienne BeuronDivision of Structural Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Nora B CroninDivision of Structural Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Edward P MorrisDivision of Structural Biology, The Institute of Cancer Research, London, SW3 6JB, UK. ed.morris@icr.ac.uk.ORCID http://orcid.org/0000-0003-3544-0041
Argyris PolitisDepartment of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK. argyris.politis@kcl.ac.uk.ORCID http://orcid.org/0000-0002-1617-4238
King's College London · GBInstitute of Cancer Research · GBConsejo Superior de Investigaciones Científicas · ESMartin Luther University Halle-Wittenberg · DE

Funding

Cancer Research UK 16749Wellcome Trust
6 · The paper itself

Abstract

Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCOP9 Signalosome ComplexCryoelectron MicroscopyIntracellular Signaling Peptides and ProteinsMass SpectrometryNEDD8 ProteinPeptide HydrolasesProtein Processing, Post-TranslationalRecombinant ProteinsSf9 CellsUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingCOP9 Signalosome ComplexCOPS5 protein, humanCOPS6 protein, humanCULL-RING ligase, humanIntracellular Signaling Peptides and ProteinsNEDD8 ProteinNEDD8 protein, humanPeptide HydrolasesRecombinant ProteinsUbiquitin-Protein Ligases

Identifiers

PMID31444342
PMCPMC6707232
OpenAlexW2969871064

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.