Evidence map›Paper›PMID 40880185›Full record

ArticleProtein science : a publication of the Protein Society2025

An alternative pocket for binding the N-degrons by the UBR1 and UBR2 ubiquitin E3 ligases.

Shih-Ting Huang, Dai-Hua Chen, Tianchen Ren, Nicole Thomas, Jian Wu, Banumathi Sankaran, Renee Jones, Susan Taylor, Yuan Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein science : a publication of the Protein Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. An alternative pocket for binding the N-degrons by the UBR1 and UBR2 ubiquitin E3 ligases.Protein science : a publication of the Protein Society · 2025
    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

9 authors.

Shih-Ting HuangDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
Dai-Hua ChenDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Tianchen RenDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
Nicole ThomasDivision of Surgical Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.
Jian WuDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
Banumathi SankaranMolecular Biophysics and Integrated Bioimaging Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Renee JonesDivision of Surgical Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.
Susan TaylorDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA.
Yuan ChenDivision of Surgical Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0002-1510-182X

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
Lessons Learned from PKA: Assembly of Dynamic Macromolecular SwitchesR35GM130389 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUSAN S. TAYLOR · 2019 to 2026
$5.7M
Targeting c-Myc and Proteasome Inhibitor Resistance in Multiple MyelomaR01CA212119 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, YUAN · 2017 to 2021
$2.8M
SUMO Modification and Cancer TherapyR01CA265410 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, YUAN · 2021 to 2025
$2.5M
National Institutes of Health, National Institute of General Medical Sciences P30 GM124169-01NCI NIH HHS R01 CA212119NCI NIH HHS R01 CA265410NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R35 GM130389NIH HHS R01CA212119NIH HHS R01CA265410U.S. Department of Defense HT9425-23-1-0560U.S. Department of Defense PA220024P1
6 · The paper itself

Abstract

The UBR family of ubiquitin ligases binds to N-termini of their targets (known as N-degron) to induce their ubiquitination and degradation via a conserved domain known as UBR-box. UBR1 and UBR2 share the highest sequence homology among the family, and substantial structural studies were previously performed for substrate binding by the UBR-boxes of UBR1 and UBR2. Here, we describe a new pocket in the UBR-boxes of UBR1 and UBR2 for binding the second residues of N-degrons through determining five co-crystal structures of the UBR-boxes with various N-degron peptides. Together with binding affinities measured by fluorescence polarization, we show that the two highly homologous UBR-boxes can interact with the second residue of an N-degron differently. In addition, the UBR-boxes undergo different conformational changes when binding N-degrons. Furthermore, we demonstrate that the sidechain of the third amino acid of an N-degron has no contribution to binding the UBR-boxes. These findings represent a new conceptual advancement for the UBR E3 ligases and the new insights described here can be leveraged for developing their selective ligands for research and potential therapies.

Indexed as

Saccharomyces cerevisiae ProteinsUbiquitin-Protein LigasesBinding SitesCrystallography, X-RayDegronsHumansModels, MolecularProtein BindingSaccharomyces cerevisiae ProteinsUbiquitin-Protein Ligasescrystal structurefluorescence polarizationN‐end ruleubiquitinUBR1UBR2

Identifiers

PMID40880185
PMCPMC12304086

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.