ArticleScience advances2023
Saturation mutagenesis of α-synuclein reveals monomer fold that modulates aggregation.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reverse-engineering amyloid strains with generative protein design.bioRxiv : the preprint server for biology · 2026Article
- Mutational Scanning of α-Synuclein using a Clickable Protein Tag Reveals Determinants of Membrane-Induced Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Concentration-dependent mutational scanning probes the cellular folding landscape of α-synuclein in yeast.Protein science : a publication of the Protein Society · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Concentration-Dependent Mutational Scanning Probes the Cellular Folding Landscape of α-Synuclein in Yeast.bioRxiv : the preprint server for biology · 2025Article
- DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.bioRxiv : the preprint server for biology · 2025Article
- Lipidic folding pathway of α-Synuclein via a toxic oligomer.Nature communications · 2025Article
- Exploring the Impact of Physiological C-Terminal Truncation on α-Synuclein Conformations to Unveil Mechanisms Regulating Pathological Aggregation.Journal of chemical information and modeling · 2024Article
- Review
- In cell NMR reveals cells selectively amplify and structurally remodel amyloid fibrils.bioRxiv : the preprint server for biology · 2024Article
- Residues 2 to 7 of α-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ensemble-based design of tau to inhibit aggregation while preserving biological activity.Research square · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
α-Synuclein (aSyn) aggregation underlies neurodegenerative synucleinopathies. aSyn seeds are proposed to replicate and propagate neuronal pathology like prions. Seeding of aSyn can be recapitulated in cellular systems of aSyn aggregation; however, the mechanism of aSyn seeding and its regulation are not well understood. We developed an mEos-based aSyn seeding assay and performed saturation mutagenesis to identify with single-residue resolution positive and negative regulators of aSyn aggregation. We not only found the core regions that govern aSyn aggregation but also identified mutants outside of the core that enhance aggregation. We identified local structure within the N terminus of aSyn that hinders the fibrillization propensity of its aggregation-prone core. Based on the screen, we designed a minimal aSyn fragment that shows a ~4-fold enhancement in seeding activity and enabled discrimination of synucleinopathies. Our study expands the basic knowledge of aSyn aggregation and advances the design of cellular systems of aSyn aggregation to diagnose synucleinopathies based on protein conformation.
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