ArticleProceedings of the National Academy of Sciences of the United States of America2012
Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 73 citations in OpenAlex.
- Direct observation and quantification of single nanocondensates of the low complexity domain of TDP-43.Nature communications · 2026Article
- α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice.NPJ Parkinson's disease · 2024Article
- Solvent accessible surface area-assessed molecular basis of osmolyte-induced protein stability.RSC advances · 2024Article
- α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice.bioRxiv : the preprint server for biology · 2024Article
- Highly tunable bimane-based fluorescent probes: design, synthesis, and application as a selective amyloid binding dye.Chemical science · 2024Article
- Association of Trimethylamine N-Oxide with Normal Aging and Neurocognitive Disorders: A Narrative Review.Brain sciences · 2022Review
- The Proteome Folding Problem and Cellular Proteostasis.Journal of molecular biology · 2021Review
- Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly.International journal of molecular sciences · 2021Article
- Untangling the interaction of α-synuclein with DNA i-motifs and hairpins by volume-sensitive single-molecule FRET spectroscopy.RSC chemical biology · 2021Article
- Single Molecule Characterization of Amyloid Oligomers.Molecules (Basel, Switzerland) · 2021Review
- Polyol and sugar osmolytes can shorten protein hydrogen bonds to modulate function.Communications biology · 2020Article
- The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes.The Journal of cell biology · 2020Article
- Effect of Osmolytes on Conformational Behavior of Intrinsically Disordered Protein α-Synuclein.Biophysical journal · 2019Article
- Single-molecule fluorescence studies of intrinsically disordered proteins and liquid phase separation.Biochimica et biophysica acta. Proteins and proteomics · 2019Review
- Polymer effects modulate binding affinities in disordered proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A Chemical Chaperone Decouples TDP-43 Disordered Domain Phase Separation from Fibrillation.Biochemistry · 2018Article
- Origin of Internal Friction in Disordered Proteins Depends on Solvent Quality.The journal of physical chemistry. B · 2018Article
- Small Molecules Attenuate the Interplay between Conformational Fluctuations, Early Oligomerization and Amyloidosis of Alpha Synuclein.Scientific reports · 2018Article
- Fluorescence spectroscopy reveals N-terminal order in fibrillar forms of α-synuclein.Chemical communications (Cambridge, England) · 2018Article
- Using a FRET Library with Multiple Probe Pairs To Drive Monte Carlo Simulations of α-Synuclein.Biophysical journal · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson's disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 21 [urea][TMAO] ratio has a net neutral effect on the protein's dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments.
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