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Updated: Jun 27, 2026
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Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
Published on: June 23, 2022
Fast amide proton exchange reveals close relation between native-state dynamics and unfolding kinetics
Hagen Hofmann1, Ulrich Weininger, Christian Löw
1Institute of Biochemistry and Biotechnology, Institute of Physics, Biophysics group and Mitteldeutsches Zentrum für Struktur and Dynamik der Proteine (MZP), Martin-Luther University Halle-Wittenberg, 06099 Halle.
Journal of the American Chemical Society
|December 9, 2008
Summary
Protein unfolding pathways are linked to native-state dynamics. We identified dynamic heterogeneity in barstar
Area of Science:
- Protein dynamics
- Protein folding and unfolding
- Biophysics
Background:
- Proteins often fold/unfold via partially structured intermediates.
- The reasons for two-state vs. non-two-state unfolding remain unclear.
Purpose of the Study:
- To investigate the unfolding pathway of the small protein barstar.
- To correlate unfolding mechanisms with native-state dynamics.
Main Methods:
- Fast proton-exchange experiments to identify native-state dynamics.
- Stopped-flow fluorescence to detect unfolding kinetics.
- Comparative analysis of experimental data.
Main Results:
- Extensive dynamic heterogeneity was found within the native-state ensemble of barstar.
- Helix 3 dynamics were cooperative but decoupled from global dynamics.
- Unfolding initiates with helix 3, followed by tertiary structure breakdown.
Conclusions:
- Barstar's unfolding pathway is closely coupled to its native-state dynamics.
- Native-state dynamics provide insights into protein unfolding mechanisms.
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