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Non-native interactions are critical for mechanical strength in PKD domains
Julia R Forman1, Zu Thur Yew2, Seema Qamar3
1Cambridge University Chemical Laboratory, MRC Centre for Protein Engineering, Lensfield Road, Cambridge, CB2 1EW, UK.
Structure (London, England : 1993)
|December 17, 2009
Summary
Protein mechanical strength is often determined by native structure. However, polycystin-1 PKD domains gain strength from force-induced nonnative interactions, revealing a novel mechanism for protein stability.
Area of Science:
- Biophysics
- Structural Biology
- Mechanobiology
Background:
- Protein mechanical strength is typically attributed to native state topology.
- Polycystin-1 PKD domains exhibit greater mechanical strength than predicted by their native structures.
Purpose of the Study:
- To investigate the role of nonnative interactions in the mechanical stability of polycystin-1 PKD domains.
- To test the hypothesis that force-induced structural rearrangement enhances protein mechanical strength.
Main Methods:
- Utilized molecular dynamics simulations to model protein behavior under force.
- Introduced specific mutations to disrupt nonnative hydrogen bond formation.
- Assessed the impact of mutations on the mechanical stability of PKD domains.
Main Results:
- Mutations designed to prevent nonnative interactions significantly reduced mechanical stability.
- These mutations only moderately destabilized the native state, highlighting the importance of nonnative interactions.
- Force-induced conformational changes lead to the formation of stabilizing nonnative interactions.
Conclusions:
- Nonnative interactions play a crucial role in imparting significant mechanical stability to polycystin-1 PKD domains.
- This force-induced stabilization mechanism is essential for the mechanosensor function of polycystin-1.
- The application of force can paradoxically strengthen protein structures through nonnative interactions.
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