Evidence map›Paper›PMID 38326650›Full record

ArticleNature structural & molecular biology2024

Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases.

Joanna Liwocha, Jerry Li, Nicholas Purser, Chutima Rattanasopa, Samuel Maiwald, David T Krist, Daniel C Scott, Barbara Steigenberger, J Rajan Prabu, Brenda A Schulman and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
9.4field-weighted citation impact, top 1% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
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  8. Article
  9. E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  10. Article
  11. Design and Semisynthesis of Ubiquitin Extension Probes.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  12. Review
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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

11 authors at 3 institutions in 2 countries.

Joanna Liwocha *Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID http://orcid.org/0000-0002-8341-8466
Jerry Li *Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, Las Vegas, NV, USA.ORCID http://orcid.org/0000-0003-4036-2471
Nicholas PurserDepartment of Chemistry and Biochemistry, University of Nevada, Las Vegas, Las Vegas, NV, USA.
Chutima RattanasopaDepartment of Chemistry and Biochemistry, University of Nevada, Las Vegas, Las Vegas, NV, USA.
Samuel MaiwaldDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.
David T KristDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.
Daniel C ScottDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Barbara SteigenbergerMass Spectrometry Core Facility, Max Planck Institute of Biochemistry, Martinsried, Germany.
J Rajan PrabuDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID http://orcid.org/0000-0002-7726-9310
Brenda A SchulmanDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany. schulman@biochem.mpg.de.ORCID http://orcid.org/0000-0002-3083-1126
Gary KleigerDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany. gary.kleiger@unlv.edu.ORCID http://orcid.org/0000-0003-3924-1680
Max Planck Institute of Biochemistry · DEUniversity of Nevada, Las Vegas · USSt. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
How ubiquitin-carrying enzymes contribute to ubiquitin ligase specificityR01GM141409 · NIGMS · UNIVERSITY OF NEVADA LAS VEGAS · PI KLEIGER, GARY L. · 2021 to 2024
$1.6M
NCI NIH HHS P30 CA021765NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R01 GM141409
6 · The paper itself

Abstract

E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked poly-ubiquitin chains to control an enormous swath of eukaryotic biology. Yet the molecular mechanisms underlying this exceptional linkage specificity and millisecond kinetics of poly-ubiquitylation remain unclear. Here we obtain cryogenic-electron microscopy (cryo-EM) structures that provide pertinent insight into how such poly-ubiquitin chains are forged. The CRL RING domain not only activates the E2-bound ubiquitin but also shapes the conformation of a distinctive UBE2R2 loop, positioning both the ubiquitin to be transferred and the substrate-linked acceptor ubiquitin within the active site. The structures also reveal how the ubiquitin-like protein NEDD8 uniquely activates CRLs during chain formation. NEDD8 releases the RING domain from the CRL, but unlike previous CRL-E2 structures, does not contact UBE2R2. These findings suggest how poly-ubiquitylation may be accomplished by many E2s and E3s.

Indexed as

Cullin ProteinsUbiquitin-Conjugating EnzymesPolyubiquitinUbiquitinUbiquitinationUbiquitin-Protein LigasesCullin ProteinsPolyubiquitinUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID38326650
PMCPMC10873206
OpenAlexW4391630673

What OpenQuestion holds

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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 OpenQuestion graph.