Evidence map›Paper›PMID 23550736›Full record

ArticleBiochemistry2013

Activation of UbcH5c~Ub is the result of a shift in interdomain motions of the conjugate bound to U-box E3 ligase E4B.

Sarah E Soss, Rachel E Klevit, Walter J Chazin

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. How to Inactivate Human Ubiquitin E3 Ligases by Mutation.Frontiers in cell and developmental biology · 2020
    Review
  10. Article
  11. Enzymatic Logic of Ubiquitin Chain Assembly.Frontiers in physiology · 2019
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

3 authors at 2 institutions in 1 country.

Sarah E SossDepartment of Biochemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
Rachel E Klevit
Walter J Chazin
Vanderbilt University · USUniversity of Washington · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jin Chen · 1995 to 2026
$172.8M
BIOCHEMICAL &CHEMICAL TRAINING FOR CANCER RESEARCHT32CA009582 · NCI · VANDERBILT UNIVERSITY · PI David K Cortez · 1987 to 2026
$8.8M
Structural and Functional Characterization of BRCA1/BARD1R01GM088055 · NIGMS · UNIVERSITY OF WASHINGTON · PI KLEVIT, RACHEL E · 2009 to 2020
$6.5M
Structural Biology of U-box E3 Ubiquitin LigasesR01GM075156 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 2005 to 2013
$2.4M
Console upgrades for biological NMR spectrometersS10RR025677 · NCRR · VANDERBILT UNIVERSITY · PI SANDERS, CHARLES R · 2009 to 2009
$460k
NCI NIH HHS P30 CA068485NCI NIH HHS T32 CA009582NCRR NIH HHS 1S-10RR025677NCRR NIH HHS S10 RR025677NIGMS NIH HHS R01 GM075156NIGMS NIH HHS R01 GM088055
6 · The paper itself

Abstract

Post-translational modification of proteins with ubiquitin is mediated by dynamic multienzyme machinery (E1, E2, and E3). E3 ubiquitin ligases play a key role acting as both scaffolds to bring reactants together and activators to catalyze ubiquitin (Ub) transfer from E2~Ub conjugates to substrates. Our recent studies provided insights into the mechanism of the activation event; binding of an E3 to an E2~Ub conjugate was found to affect the motions of E2~Ub and allosterically stimulate Ub transfer. This proposed mechanism implies that the dynamics of the conjugate, which has been shown to occupy a wide range of E2~Ub orientations, will be altered significantly upon binding of E3. To directly assess the effect of E3 binding on E2~Ub dynamics, we undertook an in-depth comparative analysis of (15)N nuclear magnetic resonance relaxation of UbcH5c~Ub in the absence and presence of the E3 ligase, E4B. Challenges encountered in deciphering interdomain motions for this ternary complex are discussed along with the limitations of the current approaches. Notably, although a reduction in interdomain dynamics of UbcH5c~Ub is observed upon binding to E4B, Ub retains an extensive degree of flexibility. These results provide strong support for our dynamic model of a significant orientational bias of Ub toward a more closed conformation in the E3/E2~Ub complex.

Indexed as

BiocatalysisModels, MolecularNuclear Magnetic Resonance, BiomolecularProtein BindingUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUBE2D3 protein, humanUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligases

Identifiers

PMID23550736
PMCPMC3666176
OpenAlexW2055019434

What OpenQuestion holds

Textmetadata
LicenceTDM
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.