ArticleProtein science : a publication of the Protein Society2008
Hydrogen exchange of monomeric alpha-synuclein shows unfolded structure persists at physiological temperature and is independent of molecular crowding in Escherichia coli.
Article in Protein science : a publication of the Protein Society, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 99 citations in OpenAlex.
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- High-pH NMR to Identify Macromolecular Hydrogen-Bonds and Foldons.Journal of the American Chemical Society · 2026Article
- Molecular Interplay of Small Molecules and Calcium Ions with α-Synuclein Revealed by NMR and Molecular Dynamics Simulations.ACS chemical neuroscience · 2026Article
- High-pH NMR to Identify Macromolecular Hydrogen-Bonds and Foldons.bioRxiv : the preprint server for biology · 2026Article
- Water Accelerates in the Hydration Shell of the N- and C-Terminal Domains of α-Synuclein in the Presence of NaCl.The journal of physical chemistry. B · 2026Article
- From molecular descriptions to cellular functions of intrinsically disordered protein regions.Biophysics reviews · 2024Review
- Wild-Type α-Synuclein Structure and Aggregation: A Comprehensive Coarse-Grained and All-Atom Molecular Dynamics Study.Journal of chemical information and modeling · 2024Article
- Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles.Antioxidants (Basel, Switzerland) · 2023Article
- The Residual Structure of Unfolded Proteins was Elucidated from the Standard Deviation of NMR Intensity Differences.Protein and peptide letters · 2023Article
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Glycation of α-synuclein hampers its binding to synaptic-like vesicles and its driving effect on their fusion.Cellular and molecular life sciences : CMLS · 2022Article
- Radio Signals from Live Cells: The Coming of Age of In-Cell Solution NMR.Chemical reviews · 2022Review
- Pulse-field gradient nuclear magnetic resonance of protein translational diffusion from native to non-native states.Protein science : a publication of the Protein Society · 2022Article
- The contribution of electrostatics to hydrogen exchange in the unfolded protein state.Biophysical journal · 2021Article
- Ensemble description of the intrinsically disordered N-terminal domain of the Nipah virus P/V protein from combined NMR and SAXS.Scientific reports · 2020Article
- NMR as a "Gold Standard" Method in Drug Design and Discovery.Molecules (Basel, Switzerland) · 2020Review
- Article
- Sequence-Dependent Correlated Segments in the Intrinsically Disordered Region of ChiZ.Biomolecules · 2020Article
- NMR Mapping of Disordered Segments from a Viral Scaffolding Protein Enclosed in a 23 MDa Procapsid.Biophysical journal · 2019Article
- E46K-like α-synuclein mutants increase lipid interactions and disrupt membrane selectivity.The Journal of biological chemistry · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Amide proton NMR signals from the N-terminal domain of monomeric alpha-synuclein (alphaS) are lost when the sample temperature is raised from 10 degrees C to 35 degrees C at pH 7.4. Although the temperature-induced effects have been attributed to conformational exchange caused by an increase in alpha-helix structure, we show that the loss of signals is due to fast amide proton exchange. At low ionic strength, hydrogen exchange rates are faster for the N-terminal segment of alphaS than for the acidic C-terminal domain. When the salt concentration is raised to 300 mM, exchange rates increase throughout the protein and become similar for the N- and C-terminal domains. This indicates that the enhanced protection of amide protons from the C-terminal domain at low salt is electrostatic in nature. Calpha chemical shift data point to <10% residual alpha-helix structure at 10 degrees C and 35 degrees C. Conformational exchange contributions to R2 are negligible at both temperatures. In contrast to the situation in vitro, the majority of amide protons are observed at 37 degrees C in 1H-15N HSQC spectra of alphaS encapsulated within living Escherichia coli cells. Our finding that temperature effects on alphaS NMR spectra can be explained by hydrogen exchange obviates the need to invoke special cellular factors. The retention of signals is likely due to slowed hydrogen exchange caused by the lowered intracellular pH of high-density E. coli cultures. Taken together, our results emphasize that alphaS remains predominantly unfolded at physiological temperature and pH-an important conclusion for mechanistic models of the association of alphaS with membranes and fibrils.
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