ArticleProtein science : a publication of the Protein Society2018
Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding.
Article in Protein science : a publication of the Protein Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- A single-domain antibody targets aggregation-prone region of α-synuclein to reduce synucleinopathy, rescue neurodegeneration and improve function.bioRxiv : the preprint server for biology · 2026Article
- Clemastine alleviates Parkinson's disease pathology by activating the AMPK/mTOR pathway and enhancing autophagic flux.Frontiers in aging neuroscience · 2026Article
- Specific proteolysis mediated by a p97-directed proteolysis-targeting chimera (p97-PROTAC).eLife · 2025Article
- Synuclein Proteoforms: Role in Health and Disease.Molecular neurobiology · 2025Review
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Phosphatidylinositol-3,4,5-trisphosphate interacts with alpha-synuclein and initiates its aggregation and formation of Parkinson's disease-related fibril polymorphism.Acta neuropathologica · 2023Article
- Specific Detection of Physiological S129 Phosphorylated α-Synuclein in Tissue Using Proximity Ligation Assay.Journal of Parkinson's disease · 2023Article
- Article
- Alpha-Synuclein Aggregation Pathway in Parkinson's Disease: Current Status and Novel Therapeutic Approaches.Cells · 2022Review
- Phosphorylation of CAP1 regulates lung cancer proliferation, migration, and invasion.Journal of cancer research and clinical oncology · 2022Article
- Deciphering the Structure and Formation of Amyloids in Neurodegenerative Diseases With Chemical Biology Tools.Frontiers in chemistry · 2022Review
- Applications of nanobodies in brain diseases.Frontiers in immunology · 2022Review
- Domain-Independent Inhibition of CBP/p300 Attenuates α-Synuclein Aggregation.ACS chemical neuroscience · 2021Article
- In vivo aggregation of presynaptic alpha-synuclein is not influenced by its phosphorylation at serine-129.Neurobiology of disease · 2021Article
- Nanobodies Right in the Middle: Intrabodies as Toolbox to Visualize and Modulate Antigens in the Living Cell.Biomolecules · 2020Review
- Deciphering protein post-translational modifications using chemical biology tools.Nature reviews. Chemistry · 2020Review
- Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity.Nature communications · 2020Article
- Targeting α-synuclein for PD Therapeutics: A Pursuit on All Fronts.Biomolecules · 2020Review
- In Search of Effective Treatments Targeting α-Synuclein Toxicity in Synucleinopathies: Pros and Cons.Frontiers in cell and developmental biology · 2020Review
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11 authors.
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Abstract
Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson's disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major modulators of its structure, function, degradation and toxicity. Among these PTMs, phosphorylation near the C-terminus at S129 has emerged as a dominant pathogenic modification as it is consistently observed to occur within the brain and cerebrospinal fluid (CSF) of post-mortem PD patients, and its level appears to correlate with disease progression. Phosphorylation at the neighboring tyrosine residue Y125 has also been shown to protect against α-synuclein toxicity in a Drosophila model of PD. In the present study we address the potential roles of C-terminal phosphorylation in modulating the interaction of α-synuclein with other protein partners, using a single domain antibody fragment (NbSyn87) that binds to the C-terminal region of α-synuclein with nanomolar affinity. The results reveal that phosphorylation at S129 has negligible effect on the binding affinity of NbSyn87 to α-synuclein while phosphorylation at Y125, only four residues away, decreases the binding affinity by a factor of 400. These findings show that, despite the fact that α-synuclein is intrinsically disordered in solution, selective phosphorylation can modulate significantly its interactions with other molecules and suggest how this particular form of modification could play a key role in regulating the normal and aberrant function of α-synuclein.
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