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Protein folding and unfolding on a complex energy landscape
D T Leeson1, F Gai, H M Rodriguez
1Center for Nonlinear Studies, MS B258, and Bioscience Division, MS J586, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Summary
Protein unfolding pathways can be selected by altering initial conditions. Experiments show that both barrier crossing and downhill unfolding occur simultaneously in protein ensembles.
Area of Science:
- Biophysics
- Protein dynamics
- Chemical kinetics
Background:
- Protein folding theories propose diverse conformational routes.
- Understanding these pathways is crucial for protein function and misfolding diseases.
Purpose of the Study:
- To introduce a novel kinetics experiment to probe protein unfolding pathways.
- To demonstrate pathway selection by varying initial reaction conditions.
- To investigate the simultaneous occurrence of different unfolding mechanisms.
Main Methods:
- Utilizing laser-induced temperature jump relaxation kinetics.
- Analyzing the major cold shock protein of Escherichia coli (CspA).
- Comparing kinetics for small versus large temperature jumps.
Main Results:
- Small temperature jumps show exponential kinetics, indicating a two-state folding mechanism.
- Large temperature jumps result in nonexponential kinetics, suggesting multiple unfolding pathways.
- Evidence supports the simultaneous occurrence of barrier-crossing and downhill unfolding.
Conclusions:
- Initial conditions can dictate the unfolding pathway of proteins.
- Protein ensembles can exhibit multiple simultaneous unfolding mechanisms.
- The study provides experimental criteria for observing diverse unfolding pathways.