Evidence map›Paper›PMID 27732584›Full record

ArticleNature2016

Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne.

Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, Paul P Geurink, Sarah L Maslen, Malte Gersch, Paul R Elliott, John E Burke, Bianca D M van Tol, Masato Akutsu and 5 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
8.7field-weighted citation impact, top 2% 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

94 citing papers in PubMed, 158 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Internal Ubiquitin Electrophiles for Covalent Trapping and Inhibition of Deubiquitinases.Chembiochem : a European journal of chemical biology · 2025
    Article
  9. Article
  10. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  11. Article
  12. The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

34 more citing papers are in PubMed but not listed here.

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

15 authors at 4 institutions in 3 countries.

Tycho E T MevissenMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Yogesh Kulathu *Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Monique P C Mulder *Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Paul P GeurinkDivision of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Sarah L MaslenMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Malte GerschMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Paul R ElliottMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
John E BurkeMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Bianca D M van TolDivision of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Masato AkutsuMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Farid El OualidDivision of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Masato KawasakiStructural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan.
Stefan M V FreundMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Huib OvaaDivision of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
David KomanderMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Medical Research Council · GBThe Netherlands Cancer Institute · NLMRC Laboratory of Molecular Biology · GBHigh Energy Accelerator Research Organization · JP

Funding

British Heart Foundation PG/11/109/29247European Research Council 309756Medical Research Council MC_U105184308Medical Research Council MC_U105192732
6 · The paper itself

Abstract

The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system. Here we reveal how the deubiquitinase Cezanne (also known as OTUD7B) specifically targets Lys11-linked polyubiquitin. Crystal structures of Cezanne alone and in complex with monoubiquitin and Lys11-linked diubiquitin, in combination with hydrogen-deuterium exchange mass spectrometry, enable us to reconstruct the enzymatic cycle in great detail. An intricate mechanism of ubiquitin-assisted conformational changes activates the enzyme, and while all chain types interact with the enzymatic S1 site, only Lys11-linked chains can bind productively across the active site and stimulate catalytic turnover. Our work highlights the plasticity of deubiquitinases and indicates that new conformational states can occur when a true substrate, such as diubiquitin, is bound at the active site.

Indexed as

BiocatalysisCatalytic DomainCrystallography, X-RayDeubiquitinating EnzymesDeuterium Exchange MeasurementEndopeptidasesEnzyme ActivationHumansLysineMass SpectrometryModels, MolecularPolyubiquitinProtein BindingProtein ConformationSubstrate SpecificityUbiquitinationDeubiquitinating EnzymesEndopeptidasesLysineOTUD7B protein, humanPolyubiquitinUbiquitins

Identifiers

PMID27732584
PMCPMC5295632
OpenAlexW2530082208

What OpenQuestion holds

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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.