The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis
Open accessAbstract
Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING domain of rat RNF4 in complex with E2 (UbcH5A) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The carboxy-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilize the consequent tetrahedral transition-state intermediate.
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“Compared to prior isolated RING-UBE2D~UB structures28–30, the neddylated CRL1β-TRCP-UBE2D~UB-substrate intermediate shows additional density corresponding to the substrate proxy along a trajectory to the ubiquitylation active site”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [29]
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RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
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Metadata
- Authors
- Plechanovová, A., Jaffray, E. G., Tatham, M. H., Naismith, J. H., & Hay, R. T.
- Affiliations
- University of Dundee (GB)
- University of St Andrews (GB)
- Corresponding author
- Hay, Ronald T.
- Venue
- Nature
- Published
- 2012-07-29
- Volume
- 489
- Issue
- 7414
- Pages
- 115-120
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3442243
- OpenAlex
- W2147542927
- Cited by
- 521
- References
- 41
- Citations by year
- 2026: 25 · 2025: 36 · 2024: 41 · 2023: 24 · 2022: 41 · 2021: 39 · 2020: 41 · 2019: 29 · 2018: 27 · 2017: 44 · 2016: 39 · 2015: 37 · 2014: 47 · 2013: 46 · 2012: 5
- FWCI
- 17.37
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Wellcome Trust (098391, 081862, 098391/Z/12/Z)
- Cancer Research UK (13067)
- Scottish Funding Council
- 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
- RING E3 ubiquitin ligase, RNF4, UbcH5a, ubiquitin transfer, isopeptide bonds, ubiquitin binding, crystal structure
- MeSH terms
- Animals, Humans, Hydrolysis, Models, Molecular, Mutation, Nuclear Proteins, Protein Binding, Transcription Factors, Zinc Fingers, Protein Structure, Tertiary, Crystallography, X-Ray, Catalytic Domain, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Multiprotein Complexes, Rats, Ubiquitination, Biocatalysis
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