ArticleProceedings of the National Academy of Sciences of the United States of America2010
Identification of a helical intermediate in trifluoroethanol-induced alpha-synuclein aggregation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 173 citations in OpenAlex.
- Solution NMR reveals micelle-stabilized α-helical segments flanking the RIPK1 RHIM amyloid core.Biochemical and biophysical research communications · 2026Article
- Conformational landscapes of rigid and flexible molecules explored with variable temperature ion mobility-mass spectrometry.Nature communications · 2025Article
- Characterization of α-synuclein oligomers formed in the presence of lipid vesicles.Biochemistry and biophysics reports · 2024Article
- Lipid-induced polymorphic amyloid fibril formation by α-synuclein.Protein science : a publication of the Protein Society · 2023Article
- Trifluoroethanol and the behavior of a tardigrade desiccation-tolerance protein.Protein science : a publication of the Protein Society · 2023Article
- Toxic Misfolded Transthyretin Oligomers with Different Molecular Conformations Formed through Distinct Oligomerization Pathways.Biochemistry · 2022Article
- An Update on the Critical Role of α-Synuclein in Parkinson's Disease and Other Synucleinopathies: from Tissue to Cellular and Molecular Levels.Molecular neurobiology · 2022Review
- Characterization of Amyloidogenic Peptide Aggregability in Helical Subspace.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Dual Effects of Presynaptic Membrane Mimetics onFrontiers in cell and developmental biology · 2022Article
- Article
- A generic approach to decipher the mechanistic pathway of heterogeneous protein aggregation kinetics.Chemical science · 2021Article
- Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The folding propensity of α/sulfono-γ-AA peptidic foldamers with both left- and right-handedness.Communications chemistry · 2021Article
- The amphibian antimicrobial peptide uperin 3.5 is a cross-α/cross-β chameleon functional amyloid.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Fast kinetics of environmentally induced α-synuclein aggregation mediated by structural alteration in NAC region and result in structure dependent cytotoxicity.Scientific reports · 2020Article
- Evaluation of Peptide/Protein Self-Assembly and Aggregation by Spectroscopic Methods.Molecules (Basel, Switzerland) · 2020Review
- The emerging role of α-synuclein truncation in aggregation and disease.The Journal of biological chemistry · 2020Review
- Long-range Regulation of Partially Folded Amyloidogenic Peptides.Scientific reports · 2020Article
- Drug Conjugation Induced Modulation of Structural and Membrane Interaction Features of Cationic Cell-Permeable Peptides.International journal of molecular sciences · 2020Article
- Membrane interactions of intrinsically disordered proteins: The example of alpha-synuclein.Biochimica et biophysica acta. Proteins and proteomics · 2019Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Because oligomers and aggregates of the protein α-synuclein (αS) are implicated in the initiation and progression of Parkinson's disease, investigation of various αS aggregation pathways and intermediates aims to clarify the etiology of this common neurodegenerative disorder. Here, we report the formation of short, flexible, β-sheet-rich fibrillar species by incubation of αS in the presence of intermediate (10-20% v/v) concentrations of 2,2,2-trifluoroethanol (TFE). We find that efficient production of these TFE fibrils is strongly correlated with the TFE-induced formation of a monomeric, partly helical intermediate conformation of αS, which exists in equilibrium with the natively disordered state at low [TFE] and with a highly α-helical conformation at high [TFE]. This partially helical intermediate is on-pathway to the TFE-induced formation of both the highly helical monomeric conformation and the fibrillar species. TFE-induced conformational changes in the monomer protein are similar for wild-type αS and the C-terminal truncation mutant αS1-102, indicating that TFE-induced structural transitions involve the N terminus of the protein. Moreover, the secondary structural transitions of three Parkinson's disease-associated mutants, A30P, A53T, and E46K, are nearly identical to wild-type αS, but oligomerization rates differ substantially among the mutants. Our results add to a growing body of evidence indicating the involvement of helical intermediates in protein aggregation processes. Given that αS is known to populate both highly and partially helical states upon association with membranes, these TFE-induced conformations imply relevant pathways for membrane-induced αS aggregation both in vitro and in vivo.
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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.