ArticleThe EMBO journal2018
Synergistic recruitment of UbcH7~Ub and phosphorylated Ubl domain triggers parkin activation.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Fluorophore placement and size impact E2 ubiquitination efficiency.The Biochemical journal · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Modulation of mitochondrial quality control in sepsis by traditional Chinese medicine: mechanistic insights and translational perspectives.Frontiers in pharmacology · 2026Review
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1.The Journal of cell biology · 2025Article
- Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.iScience · 2025Article
- ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.Nature communications · 2025Article
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025Review
- UBE2L3 Suppresses Oxidative Stress-regulated Necroptosis to Accelerate Osteosarcoma Progression.Recent patents on anti-cancer drug discovery · 2025Article
- Article
- Activation of parkin by a molecular glue.Nature communications · 2024Article
- Additional feedforward mechanism of Parkin activation via binding of phospho-UBL and RING0 ineLife · 2024Article
- Capturing the catalytic intermediates of parkin ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling.Biomolecules · 2024Article
- Parkin-mediated ubiquitination inhibits BAK apoptotic activity by blocking its canonical hydrophobic groove.Communications biology · 2023Article
- Structure-based design and characterization of Parkin-activating mutations.Life science alliance · 2023Article
- The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family.Nature communications · 2023Article
- Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain.Structure (London, England : 1993) · 2022Article
- Distinct phosphorylation signals drive acceptor versus free ubiquitin chain targeting by parkin.The Biochemical journal · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The E3 ligase parkin ubiquitinates outer mitochondrial membrane proteins during oxidative stress and is linked to early-onset Parkinson's disease. Parkin is autoinhibited but is activated by the kinase PINK1 that phosphorylates ubiquitin leading to parkin recruitment, and stimulates phosphorylation of parkin's N-terminal ubiquitin-like (pUbl) domain. How these events alter the structure of parkin to allow recruitment of an E2~Ub conjugate and enhanced ubiquitination is an unresolved question. We present a model of an E2~Ub conjugate bound to the phospho-ubiquitin-loaded C-terminus of parkin, derived from NMR chemical shift perturbation experiments. We show the UbcH7~Ub conjugate binds in the open state whereby conjugated ubiquitin binds to the RING1/IBR interface. Further, NMR and mass spectrometry experiments indicate the RING0/RING2 interface is re-modelled, remote from the E2 binding site, and this alters the reactivity of the RING2(Rcat) catalytic cysteine, needed for ubiquitin transfer. Our experiments provide evidence that parkin phosphorylation and E2~Ub recruitment act synergistically to enhance a weak interaction of the pUbl domain with the RING0 domain and rearrange the location of the RING2(Rcat) domain to drive parkin activity.
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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.