ArticleNature structural & molecular biology2017
Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Cis or trans: a puzzle of Parkin activation mechanism.Essays in biochemistry · 2026Review
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity.Cancer research · 2025Article
- Internal Ubiquitin Electrophiles for Covalent Trapping and Inhibition of Deubiquitinases.Chembiochem : a European journal of chemical biology · 2025Article
- STK4 inhibits the E3 activity of HOIP by phosphorylating its allosteric ubiquitin-binding site.Cell discovery · 2025Article
- 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
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Additional feedforward mechanism of Parkin activation via binding of phospho-UBL and RING0 ineLife · 2024Article
- Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Capturing the catalytic intermediates of parkin ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- PRKN-linked familial Parkinson's disease: cellular and molecular mechanisms of disease-linked variants.Cellular and molecular life sciences : CMLS · 2024Review
- Parkin-mediated ubiquitination inhibits BAK apoptotic activity by blocking its canonical hydrophobic groove.Communications biology · 2023Article
- Phosphorylation at Ser65 modulates ubiquitin conformational dynamics.Structure (London, England : 1993) · 2023Article
- The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family.Nature communications · 2023Article
- Characterisation of HOIP RBR E3 ligase conformational dynamics using integrative modelling.Scientific reports · 2022Article
- Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation.Human molecular genetics · 2022Article
- Distinct phosphorylation signals drive acceptor versus free ubiquitin chain targeting by parkin.The Biochemical journal · 2022Article
- Activation mechanism of PINK1.Nature · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism.
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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 OpenQuestion graph.