Evidence mapPaperPMID 40360510Full record

ArticleNature communications2025

ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.

Juraj Ahel, Arda Balci, Victoria Faas, Daniel B Grabarczyk, Roosa Harmo, Daniel R Squair, Jiazhen Zhang, Elisabeth Roitinger, Frederic Lamoliatte, Sunil Mathur and 10 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026
    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

20 authors.

Juraj AhelResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.ORCID http://orcid.org/0000-0003-0293-1063
Arda BalciMRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
Victoria FaasResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.
Daniel B GrabarczykResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.ORCID http://orcid.org/0000-0003-0216-7085
Roosa HarmoMRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
Daniel R SquairMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Jiazhen ZhangMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Elisabeth RoitingerInstitute of Molecular Biotechnology (IMBA), Vienna BioCenter, Vienna, Austria.ORCID http://orcid.org/0000-0002-3405-7801
Frederic LamoliatteMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Sunil MathurMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Luiza DeszczResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.
Lillie E BellResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.ORCID http://orcid.org/0009-0001-9398-4031
Anita LehnerVienna BioCenter Core Facilities, Vienna BioCenter, Vienna, Austria.
Thomas L WilliamsResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.
Hanna SowarMRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
Anton MeinhartResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria.
Nicola T WoodMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom.ORCID http://orcid.org/0000-0002-3347-6625
Tim ClausenResearch Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria. tim.clausen@imp.ac.at.ORCID http://orcid.org/0000-0003-1582-6924
Satpal VirdeeMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom. s.s.virdee@dundee.ac.uk.ORCID http://orcid.org/0000-0002-7052-9802
Adam J FletcherMRC University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom. adam.fletcher@glasgow.ac.uk.ORCID http://orcid.org/0000-0003-1742-6588

Funding

RCUK | MRC | Medical Research Foundation MR/T043482/1
6 · The paper itself

Abstract

The giant E3 ubiquitin ligase RNF213 is a conserved component of mammalian cell-autonomous immunity, limiting the replication of bacteria, viruses and parasites. To understand how RNF213 reacts to these unrelated pathogens, we employ chemical and structural biology to find that ATP binding to its ATPases Associated with diverse cellular Activities (AAA) core activates its E3 function. We develop methodology for proteome-wide E3 activity profiling inside living cells, revealing that RNF213 undergoes a reversible switch in E3 activity in response to cellular ATP abundance. Interferon stimulation of macrophages raises intracellular ATP levels and primes RNF213 E3 activity, while glycolysis inhibition depletes ATP and downregulates E3 activity. These data imply that ATP bears hallmarks of a danger/pathogen associated molecular pattern, coordinating cell-autonomous defence. Furthermore, quantitative labelling of RNF213 with E3-activity probes enabled us to identify the catalytic cysteine required for substrate ubiquitination and obtain a cryo-EM structure of the RNF213-E2-ubiquitin conjugation enzyme transfer intermediate, illuminating an unannotated E2 docking site. Together, our data demonstrate that RNF213 represents a new class of ATP-dependent E3 enzyme, employing distinct catalytic and regulatory mechanisms adapted to its specialised role in the broad defence against intracellular pathogens.

Indexed as

Adenosine TriphosphateUbiquitin-Protein LigasesAdenosine TriphosphatasesAnimalsHEK293 CellsHumansMacrophagesMiceUbiquitinationUbiquitin-Conjugating EnzymesAdenosine TriphosphatasesAdenosine TriphosphateUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID40360510
PMCPMC12075652

What Socratic 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 Socratic graph.