Evidence map›Paper›PMID 23349464›Full record

ArticleThe Journal of biological chemistry2013

Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.

Peter Canning, Christopher D O Cooper, Tobias Krojer, James W Murray, Ashley C W Pike, Apirat Chaikuad, Tracy Keates, Chancievan Thangaratnarajah, Viktorija Hojzan, Brian D Marsden and 4 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 162 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 1 pooled it
9.3field-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

162 citing papers in PubMed, 1 synthesis or guideline pooled it, 289 citations in OpenAlex.

  1. Pooled it
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  20. Vesicular mechanisms of drug resistance in apicomplexan parasites.Microbiology and molecular biology reviews : MMBR · 2025
    Review

102 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
    Ayinampudi, Vikram [added]
5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Peter CanningStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Christopher D O CooperStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Tobias KrojerStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
James W MurrayStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Ashley C W PikeStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Apirat ChaikuadStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Tracy KeatesStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Chancievan ThangaratnarajahStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Viktorija HojzanStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Brian D MarsdenStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Opher GileadiStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Stefan KnappStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Frank von DelftStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Alex N BullockStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom. Electronic address: alex.bullock@sgc.ox.ac.uk.
Genomics (United Kingdom) · GBUniversity of Oxford · GB

Funding

Wellcome Trust 092809Wellcome Trust 092809/Z/10/Z
6 · The paper itself

Abstract

Cullin-RING ligases are multisubunit E3 ubiquitin ligases that recruit substrate-specific adaptors to catalyze protein ubiquitylation. Cul3-based Cullin-RING ligases are uniquely associated with BTB adaptors that incorporate homodimerization, Cul3 assembly, and substrate recognition into a single multidomain protein, of which the best known are BTB-BACK-Kelch domain proteins, including KEAP1. Cul3 assembly requires a BTB protein "3-box" motif, analogous to the F-box and SOCS box motifs of other Cullin-based E3s. To define the molecular basis for this assembly and the overall architecture of the E3, we determined the crystal structures of the BTB-BACK domains of KLHL11 both alone and in complex with Cul3, along with the Kelch domain structures of KLHL2 (Mayven), KLHL7, KLHL12, and KBTBD5. We show that Cul3 interaction is dependent on a unique N-terminal extension sequence that packs against the 3-box in a hydrophobic groove centrally located between the BTB and BACK domains. Deletion of this N-terminal region results in a 30-fold loss in affinity. The presented data offer a model for the quaternary assembly of this E3 class that supports the bivalent capture of Nrf2 and reveals potential new sites for E3 inhibitor design.

Indexed as

Binding SitesCalorimetryCarrier ProteinsCrystallography, X-RayCullin ProteinsDimerizationHumansModels, MolecularMolecular ConformationPhylogenyProteasome Endopeptidase ComplexProtein BindingProtein ConformationProtein Interaction MappingProtein Structure, SecondaryProtein Structure, TertiaryCarrier ProteinsCUL3 protein, humanCullin ProteinsKLHL11 protein, humanProteasome Endopeptidase ComplexUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID23349464
PMCPMC3597819
OpenAlexW2029330932

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.