ArticleeLife2013
Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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.
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.
Who cites it
119 citing papers in PubMed, 168 citations in OpenAlex.
- Extended motif recognition tunes WW domain affinity in MAGI-IQSEC complexes.The FEBS journal · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- Review
- Structure and mechanism of the HECT ligase HECTD3.Nature communications · 2026Article
- Structure-guided analysis and prediction of human E2-E3 ligase pairing specificity.bioRxiv : the preprint server for biology · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1.Nature communications · 2025Article
- TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains.Nature structural & molecular biology · 2025Article
- Article
- Structural visualization of HECT-type E3 ligase Ufd4 accepting and transferring ubiquitin to form K29/K48-branched polyubiquitination.Nature communications · 2025Article
- Activity-based protein profiling reveals both canonical and novel ubiquitin pathway enzymes in Plasmodium.PLoS pathogens · 2025Article
- Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.Structure (London, England : 1993) · 2025Article
- Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025Review
- Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma.Frontiers in oncology · 2025Review
- Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases.Nature communications · 2024Article
- Protein semisynthesis reveals plasticity in HECT E3 ubiquitin ligase mechanisms.Nature chemistry · 2024Article
- Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2.Nature communications · 2024Article
- Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin intermediate, which promote formation of a transient, thioester-bonded HECT∼ubiquitin intermediate. Here we report that the second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. The structure of a chemically trapped proxy for an E3∼ubiquitin-substrate intermediate reveals three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3∼ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize target lysines for ubiquitination. The data allow visualization of an E2-to-E3-to-substrate ubiquitin transfer cascade, and show how HECT-specific ubiquitin interactions driving multiple reactions are repurposed by a major E3 conformational change to promote ligation. DOI:http://dx.doi.org/10.7554/eLife.00828.001.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.