ArticleNature chemical biology2020
Structural basis for RING-Cys-Relay E3 ligase activity and its role in axon integrity.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Article
- Ubiquitin beyond the proteome: lipids, glycans, metabolites, nucleic acids, and an expanding molecular landscape.Biochemical Society transactions · 2026Review
- Ubiquitin E3 ligase MYCBP2 targets KIF14 and contributes to acute myeloid leukemia progression.The Journal of biological chemistry · 2026Article
- Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Design and Semisynthesis of Ubiquitin Extension Probes.Methods in molecular biology (Clifton, N.J.) · 2026Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.Nature communications · 2025Article
- Transcription of Clock Genes in Medulloblastoma.Cancers · 2025Article
- Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025Review
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
- Emerging roles for E3 ubiquitin ligases in neural development and disease.Frontiers in cell and developmental biology · 2025Review
- Ubiquitin E3 ligases in the plant Arg/N-degron pathway.The Biochemical journal · 2024Review
- Determinants of chemoselectivity in ubiquitination by the J2 family of ubiquitin-conjugating enzymes.The EMBO journal · 2024Article
- Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogenesis and prevent obesity.Signal transduction and targeted therapy · 2024Article
- Design and Semisynthesis of Biselectrophile-Functionalized Ubiquitin Probes To Investigate Transthioesterification Reactions.Organic letters · 2024Article
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4.Nature structural & molecular biology · 2024Article
- HDAC7 drives glioblastoma to a mesenchymal-like state via LGALS3-mediated crosstalk between cancer cells and macrophages.Theranostics · 2024Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
MYCBP2 is a ubiquitin (Ub) E3 ligase (E3) that is essential for neurodevelopment and regulates axon maintenance. MYCBP2 transfers Ub to nonlysine substrates via a newly discovered RING-Cys-Relay (RCR) mechanism, where Ub is relayed from an upstream cysteine to a downstream substrate esterification site. The molecular bases for E2-E3 Ub transfer and Ub relay are unknown. Whether these activities are linked to the neural phenotypes is also unclear. We describe the crystal structure of a covalently trapped E2~Ub:MYCBP2 transfer intermediate revealing key structural rearrangements upon E2-E3 Ub transfer and Ub relay. Our data suggest that transfer to the dynamic upstream cysteine, whilst mitigating lysine activity, requires a closed-like E2~Ub conjugate with tempered reactivity, and Ub relay is facilitated by a helix-coil transition. Furthermore, neurodevelopmental defects and delayed injury-induced degeneration in RCR-defective knock-in mice suggest its requirement, and that of substrate esterification activity, for normal neural development and programmed axon degeneration.
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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.