The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Structural Basis for Cul3 Protein Assembly with the BTB-Kelch Family of E3 Ubiquitin Ligases
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Accordingly, Keap1 contains three functional domains (Figure 5). The N-terminal BTB (broad complex, tramtrack, and bric à brac) domain mediates Keap1 homodimerization and contributes to its interaction with Cul3 [68]. Additional Cul3 interaction is provided by a 3-box motif found within the proximal part of the intervening region (IVR) [67]. The IVR contains key reactive cysteine residues through”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [67]
In the citing paper
“BTB-containing E3 ligases are typically distinguished by the presence of a 3-box motif that enables high-affinity binding of Cullin 3 (refs 74,75 ).”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [74]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915 · cited 1×
“Manual model building was performed with COOT (42) and the models refined with CNS (43, 44), REFMAC (45, 46), or BUSTER (47) using TLS and NCS restraints as appropriate.”
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · cited 2×
“Automated model building tasks were conducted with BUCCANEER (39, 40) or PHENIX.”
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,317
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,723
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,796 · cited 1×
“Manual model building was performed with COOT (42) and the models refined with CNS (43, 44), REFMAC (45, 46), or BUSTER (47) using TLS and NCS restraints as appropriate.”
MolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
Inference of Macromolecular Assemblies from Crystalline State
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 10,007 · cited 1×
“Values were calculated using the protein interfaces, surfaces, and assemblies service at the European Bioinformatics Institute (68).”
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
Flagged first, then by citations
Cited by
Sorted by citations
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway
Baird, L., & Yamamoto, M. P. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00099-20 · Cited by 1,671
The whole-genome landscape of medulloblastoma subtypes
Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Gröbner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., et al. (2017) · Nature · doi:10.1038/nature22973 · Cited by 1,112
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130
“Cul3 assembly requires a “3-box” motif that is characteristic of BTB-Kelch proteins [67].”
BackgroundInfluentialTargeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960
Self-citation
Metadata
- Authors
- Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Marsden, B. D., Gileadi, O., Knapp, S., von Delft, F., & Bullock, A. N.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Bullock, Alex N.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 288
- Issue
- 11
- Pages
- 7803-7814
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3597819
- OpenAlex
- W2029330932
- Cited by
- 284
- References
- 71
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 22 · 2023: 18 · 2022: 25 · 2021: 28 · 2020: 32 · 2019: 22 · 2018: 13 · 2017: 23 · 2016: 15 · 2015: 20 · 2014: 15 · 2013: 13
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- University of Huddersfield Repository (University of Huddersfield) (acceptedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company
- Pfizer (1097737)
- GlaxoSmithKline
- Genome Canada (1097737)
- Wellcome Trust (092809, 092809/Z/10/Z, 1097737, 092809/Z/10)
- Diamond Light Source (1097737)
- Ontario Ministry of Economic Development and Innovation (092809/Z/10/Z, 1097737)
- Ministero dello Sviluppo Economico
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- CUL3, cullin-RING ligases, protein assembly, Kelch domain, N-terminal extension, Keap1, E3 ubiquitin ligase inhibitors, crystal structure
- MeSH terms
- Binding Sites, Calorimetry, Carrier Proteins, Humans, Models, Molecular, Molecular Conformation, Phylogeny, Protein Binding, Protein Conformation, Substrate Specificity, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, Dimerization, Ubiquitin, Protein Interaction Mapping, Ubiquitin-Protein Ligases, Cullin Proteins, Proteasome Endopeptidase Complex
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
