Evidence map›Paper›PMID 40205224›Full record

ArticleNature structural & molecular biology2025

Shigella flexneri evades LPS ubiquitylation through IpaH1.4-mediated degradation of RNF213.

Katerina Naydenova, Keith B Boyle, Claudio Pathe, Prathyush Pothukuchi, Ana Crespillo-Casado, Felix Scharte, Pierre-Mehdi Hammoudi, Elsje G Otten, Neal M Alto, Felix Randow

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. RNF213-dependent lytic destruction ofProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
  3. Targeting of ELMO2 by thebioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. TheeLife · 2025
    Article
  10. HoweLife · 2025
    Article
  11. Article
  12. ThebioRxiv : the preprint server for biology · 2025
    Article
  13. Proximity biotinylation at the host-bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Autophagy and Bacterial infections.Autophagy reports · 2025
    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

10 authors.

Katerina Naydenova *Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Keith B Boyle *Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Claudio Pathe *Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Prathyush PothukuchiDivision of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Ana Crespillo-CasadoDivision of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Felix ScharteDivision of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0002-6710-9524
Pierre-Mehdi HammoudiDivision of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Elsje G OttenDivision of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0002-8716-3560
Neal M AltoDepartment of Microbiology, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-7602-3853
Felix RandowDivision of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK. randow@mrc-lmb.cam.ac.uk.ORCID http://orcid.org/0000-0003-0694-5315

Funding

Type III effector regulation of host signal transduction systemsR01AI083359 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ALTO, NEAL MATHEW · 2009 to 2024
$6.3M
Type III effector regulation of host GTPase signalingR56AI083359 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ALTO, NEAL MATHEW · 2014 to 2014
$452k
NIAID NIH HHS R01 AI083359NIAID NIH HHS R56 AI083359Wellcome Trust
6 · The paper itself

Abstract

Pathogens have evolved diverse strategies to counteract host immunity. Ubiquitylation of lipopolysaccharide (LPS) on cytosol-invading bacteria by the E3 ligase RNF213 creates 'eat me' signals for antibacterial autophagy, but whether and how cytosol-adapted bacteria avoid LPS ubiquitylation remains poorly understood. Here, we show that the enterobacterium Shigella flexneri actively antagonizes LPS ubiquitylation through IpaH1.4, a secreted effector protein with ubiquitin E3 ligase activity. IpaH1.4 binds to RNF213, ubiquitylates it and targets it for proteasomal degradation, thus counteracting host-protective LPS ubiquitylation. To understand how IpaH1.4 recognizes RNF213, we determined the cryogenic electron microscopy structure of the IpaH1.4-RNF213 complex. The specificity of the interaction is achieved through the leucine-rich repeat of IpaH1.4, which binds the RING domain of RNF213 by hijacking the conserved RING interface required for binding to ubiquitin-charged E2 enzymes. IpaH1.4 also targets other E3 ligases involved in inflammation and immunity through binding to the E2-interacting face of their RING domains, including the E3 ligase LUBAC that is required for the synthesis of M1-linked ubiquitin chains on cytosol-invading bacteria downstream of RNF213. We conclude that IpaH1.4 has evolved to antagonize multiple antibacterial and proinflammatory host E3 ligases.

Indexed as

Bacterial ProteinsLipopolysaccharidesShigella flexneriUbiquitin-Protein LigasesAntigens, BacterialCryoelectron MicroscopyDysentery, BacillaryHEK293 CellsHost-Pathogen InteractionsHumansModels, MolecularProtein BindingProteolysisUbiquitinationAntigens, BacterialBacterial ProteinsipaH protein, Shigella flexneriLipopolysaccharidesUbiquitin-Protein Ligases

Identifiers

PMID40205224
PMCPMC12440826

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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.