Evidence map›Paper›PMID 37409633›Full record

ArticleThe EMBO journal2023

Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.

Zuzana Hodáková, Irina Grishkovskaya, Hanna L Brunner, Derek L Bolhuis, Katarina Belačić, Alexander Schleiffer, Harald Kotisch, Nicholas G Brown, David Haselbach

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
6.8field-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

30 citing papers in PubMed, 44 citations in OpenAlex.

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  8. Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  18. Revisiting the structure of UBR box from human UBR6.Protein science : a publication of the Protein Society · 2025
    Article
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  20. 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

9 authors at 2 institutions in 2 countries.

Zuzana Hodáková *Research Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.ORCID 0000-0002-2599-0333
Irina Grishkovskaya *Research Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.ORCID 0000-0003-0164-9373
Hanna L BrunnerResearch Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.
Derek L BolhuisDepartment of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.ORCID 0000-0002-9062-9739
Katarina BelačićResearch Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.
Alexander SchleifferResearch Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.ORCID 0000-0001-6251-2747
Harald KotischResearch Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.ORCID 0000-0003-1684-5211
Nicholas G BrownDepartment of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.ORCID 0000-0002-6141-0164
David HaselbachResearch Institute of Molecular Pathology (IMP), ViennaBioCenter (VBC), Vienna, Austria.ORCID 0000-0002-5276-5633
Research Institute of Molecular Pathology · ATUniversity of North Carolina at Chapel Hill · US

Funding

MOLECULAR AND CELLULAR BIOPHYSICS TRAINING PROGRAMT32GM008570 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUHLMAN, BRIAN A, SLEP, KEVIN C · 1995 to 2022
$5.1M
Spindle Assembly Checkpoint SilencingR35GM128855 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Nicholas Gene Brown · 2018 to 2026
$4.1M
NIGMS NIH HHS R35 GM128855NIGMS NIH HHS T32 GM008570
6 · The paper itself

Abstract

UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin ligase has recently been identified as an important regulator of oncogenes, e.g., MYC, but little is known about its structure or mechanisms of substrate engagement and ubiquitination. Here, we present the cryo-EM structure of human UBR5, revealing an α-solenoid scaffold with numerous protein-protein interacting motifs, assembled into an antiparallel dimer that adopts further oligomeric states. Using cryo-EM processing tools, we observe the dynamic nature of the UBR5 catalytic domain, which we postulate is important for its enzymatic activity. We characterise the proteasomal nuclear import factor AKIRIN2 as an interacting protein and propose UBR5 as an efficient ubiquitin chain elongator. This preference for ubiquitinated substrates and several distinct domains for protein-protein interactions may explain how UBR5 is linked to several different signalling pathways and cancers. Together, our data expand on the limited knowledge of the structure and function of HECT E3 ligases.

Indexed as

UbiquitinUbiquitin-Protein LigasesAmino Acid MotifsCryoelectron MicroscopyHumansUbiquitinationUbiquitinUbiquitin-Protein LigasesUBR5 protein, humancryo-EMHECTUbiquitin-Proteasome systemUBR5

Identifiers

PMID37409633
PMCPMC10425842
OpenAlexW4383301919

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.