ArticleScientific reports2018
Structural insights into ubiquitin phosphorylation by PINK1.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinson's disease genomic region.Scientific reports · 2026Article
- Physical exercise as a precision strategy for targeted PINK1 recruitment- a mechanistic review.Frontiers in physiology · 2026Review
- Dynamic structural profiling of PINK1 mutations (T313M and L347P) reveals a vital molecular perturbation namely phospho-Serine 65 ubiquitin recognition point in mitophagy mediated autosomal recessive Parkinson's disease (ARPD).Frontiers in molecular neuroscience · 2026Article
- The ribosome ubiquitination code: fine-tuning translation under stress.Trends in biochemical sciences · 2025Review
- Cytosolic Delivery of Functional Ubiquitin.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Genetic Code Expansion Approaches to Decipher the Ubiquitin Code.Chemical reviews · 2024Review
- Reading and Writing the Ubiquitin Code Using Genetic Code Expansion.Chembiochem : a European journal of chemical biology · 2024Review
- Identification and structural characterization of small molecule inhibitors of PINK1.Scientific reports · 2024Article
- Interaction of PINK1 with nucleotides and kinetin.Science advances · 2024Article
- GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis.Nature communications · 2023Article
- Genetically Encoded Crosslinking Enables Identification of Multivalent Ubiquitin-Deubiquitylating Enzyme Interactions.Chembiochem : a European journal of chemical biology · 2023Article
- Article
- Targeting Mitochondria as a Therapeutic Approach for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice.NPJ Parkinson's disease · 2022Article
- Targeting Deubiquitinating Enzymes (DUBs) That Regulate Mitophagy via Direct or Indirect Interaction with Parkin.International journal of molecular sciences · 2022Review
- On the Study of Deubiquitinases: Using the Right Tools for the Job.Biomolecules · 2022Review
- The role of the individual TOM subunits in the association of PINK1 with depolarized mitochondria.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Activation mechanism of PINK1.Nature · 2022Article
- Mitophagy and Neurodegeneration: Between the Knowns and the Unknowns.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Mutations of PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin (Ub) ligase parkin can cause familial parkinsonism. These two proteins are essential for ubiquitylation of damaged mitochondria and subsequent degradation. PINK1 phosphorylates Ser65 of Ub and the Ub-like (UBL) domain of parkin to allosterically relieve the autoinhibition of parkin. To understand the structural mechanism of the Ub/UBL-specific phosphorylation by PINK1, we determined the crystal structure of Tribolium castaneum PINK1 kinase domain (TcPINK1) in complex with a nonhydrolyzable ATP analogue at 2.5 Å resolution. TcPINK1 consists of the N- and C-terminal lobes with the PINK1-specific extension. The ATP analogue is bound in the cleft between the N- and C-terminal lobes. The adenine ring of the ATP analogue is bound to a hydrophobic pocket, whereas the triphosphate group of the ATP analogue and two coordinated Mg ions interact with the catalytic hydrophilic residues. Comparison with protein kinases A and C (PKA and PKC, respectively) unveils a putative Ub/UBL-binding groove, which is wider than the peptide-binding groove of PKA or PKC to accommodate the globular head of Ub or UBL. Further crosslinking analyses suggested a PINK1-interacting surface of Ub. Structure-guided mutational analyses support the findings from the present structural analysis of PINK1.
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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.