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Hysteresis as a Marker for Complex, Overlapping Landscapes in Proteins
Benjamin T Andrews1, Dominique T Capraro, Joanna I Sulkowska
1Department of Medicinal Chemistry, University of Washington, Seattle, WA.
The Journal of Physical Chemistry Letters
|March 26, 2013
Summary
Complex proteins with challenging folding regions can exhibit hysteresis, a rare behavior. This study shows hysteresis arises from decoupled unfolding events in proteins with chromophores or knots, suggesting it may signal complex folding and functional region interplay.
Area of Science:
- Biochemistry
- Protein Folding Dynamics
- Biophysics
Background:
- Topologically complex proteins often contain 'frustrated' regions that complicate their folding pathways.
- These complex regions, while crucial for function, can lead to non-ideal folding landscapes.
- Hysteresis, a phenomenon where unfolding and folding pathways differ, is predicted to be rare but observed in certain proteins.
Purpose of the Study:
- To investigate the origins of hysteresis in protein folding.
- To explore the link between protein topology, functional regions, and folding landscape complexity.
- To determine if hysteresis can serve as an indicator of overlapping complex folding and functional regions.
Main Methods:
- Studied two protein systems: one with a fluorescent chromophore and another with a knotted topology.
- Analyzed unfolding events and their relationship to chromophore isomerization (hula-twist) and knot untying.
- Investigated the decoupling of unfolding from these specific functional events.
Main Results:
- Demonstrated that hysteresis in the studied proteins results from the decoupling of unfolding events from chromophore isomerization or knot untying.
- Showcased specific mechanisms for hysteresis in proteins with distinct topological complexities.
- Provided experimental evidence for hysteresis in proteins with functional elements that alter folding landscapes.
Conclusions:
- Hysteresis in protein folding is linked to the decoupling of unfolding from specific functional events like chromophore hula-twist or knot untying.
- This phenomenon is observed in proteins with complex topologies and functional regions.
- Hysteresis may serve as a marker for the interplay between complex protein folding landscapes and functional elements.
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