ArticleNature communications2020
Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Structures of dynamic interactors at native proteasomes by PhIX-MS and cryo-electron microscopy.Molecular cell · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Proteasome activity maintains cell-type-specific gene expression.Cell reports · 2026Article
- Autism and Human Papillomavirus (HPV) E6: A Comprehensive Review.Iranian journal of psychiatry · 2026Review
- NMR in the Age of Modern Biomedical Research and Drug Discovery.Journal of molecular biology · 2025Review
- UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome.Molecular autism · 2025Article
- Article
- An adaptive peptide-binding site in ubiquitin receptor hRpn13 revealed by structural studies.Nature communications · 2025Article
- ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.Nature communications · 2025Article
- Optimized isolation of enzymatically active ubiquitin E3 ligase E6AP/UBE3A from mammalian cells.Protein expression and purification · 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
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- Virus-host warfare by PROTACs.Nature reviews. Molecular cell biology · 2024Article
- CD28 hinge used in chimeric antigen receptor (CAR) T-cells exhibits local structure and conformational exchange amidst global disorder.Communications biology · 2024Article
- High-throughput assay exploiting disorder-to-order conformational switches: application to the proteasomal Rpn10:E6AP complex.Chemical science · 2024Article
- Discovery of reactive peptide inhibitors of human papillomavirus oncoprotein E6.Chemical science · 2023Article
- Autism-linked UBE3A gain-of-function mutation causes interneuron and behavioral phenotypes when inherited maternally or paternally in mice.Cell reports · 2023Article
- E6AP AZUL interaction with UBQLN1/2 in cells, condensates, and an AlphaFold-NMR integrated structure.Structure (London, England : 1993) · 2023Article
- Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis.Cancer biology & therapy · 2022Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Regulated proteolysis by proteasomes involves ~800 enzymes for substrate modification with ubiquitin, including ~600 E3 ligases. We report here that E6AP/UBE3A is distinguished from other E3 ligases by having a 12 nM binding site at the proteasome contributed by substrate receptor hRpn10/PSMD4/S5a. Intrinsically disordered by itself, and previously uncharacterized, the E6AP-binding domain in hRpn10 locks into a well-defined helical structure to form an intermolecular 4-helix bundle with the E6AP AZUL, which is unique to this E3. We thus name the hRpn10 AZUL-binding domain RAZUL. We further find in human cells that loss of RAZUL by CRISPR-based gene editing leads to loss of E6AP at proteasomes. Moreover, proteasome-associated ubiquitin is reduced following E6AP knockdown or displacement from proteasomes, suggesting that E6AP ubiquitinates substrates at or for the proteasome. Altogether, our findings indicate E6AP to be a privileged E3 for the proteasome, with a dedicated, high affinity binding site contributed by hRpn10.
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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.