Evidence map›Paper›PMID 36538933›Full record

ArticleMolecular cell2023

Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA.

Gus D Warren, Tomoe Kitao, Tyler G Franklin, Justine V Nguyen, Paul P Geurink, Tomoko Kubori, Hiroki Nagai, Jonathan N Pruneda

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2023. 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
5.7field-weighted citation impact, top 3% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. iScience · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. A diverse family of bacterial deubiquitinases is defined by theProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Cocrystallization of ubiquitin-deubiquitinase complexes through disulfide linkage.Acta crystallographica. Section D, Structural biology · 2023
    Article
  18. Review
  19. Article
  20. Bacterial mimicry of eukaryotic HECT ubiquitin ligation.bioRxiv : the preprint server for biology · 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

8 authors at 3 institutions in 3 countries.

Gus D WarrenDepartment of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Tomoe KitaoDepartment of Microbiology, Graduate School of Medicine, Gifu University, Gifu, Gifu 501-1194, Japan.
Tyler G FranklinDepartment of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Justine V NguyenDepartment of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Paul P GeurinkOncode Institute, Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, the Netherlands.
Tomoko KuboriDepartment of Microbiology, Graduate School of Medicine, Gifu University, Gifu, Gifu 501-1194, Japan; G-CHAIN, Gifu University, Gifu, Gifu 501-1194, Japan.
Hiroki NagaiDepartment of Microbiology, Graduate School of Medicine, Gifu University, Gifu, Gifu 501-1194, Japan; G-CHAIN, Gifu University, Gifu, Gifu 501-1194, Japan.
Jonathan N PrunedaDepartment of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: pruneda@ohsu.edu.
Oregon Health & Science University · USGifu University · JPLeiden University · NL

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3M
Exploiting bacterial effector proteins to study human ubiquitin signalingR35GM142486 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Jonathan N Pruneda · 2021 to 2026
$2.6M
NIGMS NIH HHS P30 GM133894NIGMS NIH HHS R35 GM142486
6 · The paper itself

Abstract

The versatility of ubiquitination to control vast domains of eukaryotic biology is due, in part, to diversification through differently linked poly-ubiquitin chains. Deciphering signaling roles for some chain types, including those linked via K6, has been stymied by a lack of specificity among the implicated regulatory proteins. Forged through strong evolutionary pressures, pathogenic bacteria have evolved intricate mechanisms to regulate host ubiquitin during infection. Herein, we identify and characterize a deubiquitinase domain of the secreted effector LotA from Legionella pneumophila that specifically regulates K6-linked poly-ubiquitin. We demonstrate the utility of LotA for studying K6 poly-ubiquitin signals. We identify the structural basis of LotA activation and poly-ubiquitin specificity and describe an essential "adaptive" ubiquitin-binding domain. Without LotA activity during infection, the Legionella-containing vacuole becomes decorated with K6 poly-ubiquitin as well as the AAA ATPase VCP/p97/Cdc48. We propose that LotA's deubiquitinase activity guards Legionella-containing vacuole components from ubiquitin-dependent extraction.

Indexed as

Legionella pneumophilaUbiquitinBacterial ProteinsDeubiquitinating EnzymesPolyubiquitinUbiquitinationBacterial ProteinsDeubiquitinating EnzymesPolyubiquitinUbiquitinbacterial effectordeubiquitinaseLegionella pneumophilaubiquitinVCP/p97/Cdc48

Identifiers

PMID36538933
PMCPMC9825671
OpenAlexW4312055169

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.