Evidence map›Paper›PMID 23708605›Full record

ArticleNature structural & molecular biology2013

Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal mechanism of E3 ligase shutdown.

Jeremiah J Frye, Nicholas G Brown, Georg Petzold, Edmond R Watson, Christy R R Grace, Amanda Nourse, Marc A Jarvis, Richard W Kriwacki, Jan-Michael Peters, Holger Stark and 1 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Nature structural & molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
6.7field-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

59 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Journal of medicinal chemistry · 2025
    Article
  7. Cryo-EM structures of apo-APC/C and APC/CNature communications · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Examining the mechanistic relationship of APC/CProtein science : a publication of the Protein Society · 2022
    Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Jeremiah J Frye1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nicholas G Brown
Georg Petzold
Edmond R Watson
Christy R R Grace
Amanda Nourse
Marc A Jarvis
Richard W Kriwacki
Jan-Michael Peters
Holger Stark
Brenda A Schulman
St. Jude Children's Research Hospital · USResearch Institute of Molecular Pathology · ATMax Planck Institute for Biophysical Chemistry · DEUniversity of Tennessee Health Science Center · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Mechanisms of Trauma-Induced CoagulopathyT32GM008315 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Mitchell Cohen, ELIZABETH J. KOVACS · 1991 to 2026
$7.1M
Ubiquitin-like Protein Transfer CascadesR01GM069530 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SCHULMAN, BRENDA A · 2003 to 2013
$3.4M
Structural Determinants in Cell Growth Control by p21 and p27R01CA082491 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KRIWACKI, RICHARD W · 2001 to 2011
$2.7M
Understanding the Structural Mechanism of Puma-induced ApoptosisR01GM083159 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KRIWACKI, RICHARD W · 2009 to 2012
$1.3M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA021765NCI NIH HHS P30CA021765NCI NIH HHS R01 CA082491NCI NIH HHS R01CA082491NIGMS NIH HHS 1R01GM08315NIGMS NIH HHS R01GM065930NIGMS NIH HHS R01 GM069530NIGMS NIH HHS R01 GM083159NIGMS NIH HHS T32 GM008315
6 · The paper itself

Abstract

The anaphase-promoting complex/cyclosome (APC/C) is a ~1.5-MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell-cycle regulatory proteins. Inhibition of human APC/C(CDH1) during interphase by early mitotic inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and mitosis. Here, we report a hybrid structural approach involving NMR, electron microscopy and enzymology, which reveal that EMI1's 143-residue C-terminal domain inhibits multiple APC/C(CDH1) functions. The intrinsically disordered D-box, linker and tail elements, together with a structured zinc-binding domain, bind distinct regions of APC/C(CDH1) to synergistically both block the substrate-binding site and inhibit ubiquitin-chain elongation. The functional importance of intrinsic structural disorder is explained by enabling a small inhibitory domain to bind multiple sites to shut down various functions of a 'molecular machine' nearly 100 times its size.

Indexed as

Amino Acid SequenceAnaphase-Promoting Complex-CyclosomeAntigens, CDCadherinsCell Cycle ProteinsF-Box ProteinsHumansMicroscopy, ElectronModels, MolecularMolecular Sequence DataProtein BindingProtein ConformationProtein FoldingProtein Processing, Post-TranslationalProtein Structure, TertiarySequence AlignmentAnaphase-Promoting Complex-CyclosomeAntigens, CDCadherinsCDH1 protein, humanCell Cycle ProteinsF-Box ProteinsFBXO5 protein, humanUbiquitinated ProteinsUbiquitin-Protein Ligase ComplexesUbiquitin-Protein Ligases

Identifiers

PMID23708605
PMCPMC3742808
OpenAlexW2020042573

What Socratic holds

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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.