Engineering Strategies to Overcome the Stability-Function Trade-Off in Proteins
Magdalena Teufl1,2, Charlotte U Zajc1,2, Michael W Traxlmayr1,2
1Department of Chemistry, Institute of Biochemistry, University of Natural Resources and Life Sciences, 1190 Vienna, Austria.
ACS Synthetic Biology
|March 8, 2022
Summary
Protein engineering often faces a stability-function trade-off, where improving function can decrease protein stability. This review explores strategies to overcome this challenge, enabling the creation of stable, functional proteins for applications.
Area of Science:
- Biochemistry
- Protein Engineering
- Molecular Biology
Background:
- Protein stability is crucial for biological function and applicability.
- Engineering proteins for enhanced function frequently leads to decreased stability, a phenomenon known as the stability-function trade-off.
- This trade-off arises from mutations required for functional improvements, deviating from optimized wild-type sequences.
Purpose of the Study:
- To review strategies for overcoming the stability-function trade-off in protein engineering.
- To discuss methods for generating protein variants that are both functional and stable.
- To facilitate the development of improved proteins for diverse applications.
Main Methods:
- Review of existing literature on protein engineering and stability.
- Analysis of strategies including using stable parental proteins, minimizing destabilization during functional engineering, and stability engineering of mutants.
- Discussion of library optimization and co-selection for stability and function.
Main Results:
- The stability-function trade-off is a universal challenge in protein evolution across various protein types.
- Three primary strategies effectively address this trade-off: utilizing stable scaffolds, minimizing functional engineering-induced destabilization, and repairing destabilized mutants.
- Successful implementation of these strategies aids in generating robust protein variants.
Conclusions:
- Overcoming the stability-function trade-off is essential for successful protein engineering.
- The discussed strategies provide a framework for developing stable and functional proteins.
- These advancements are critical for enhancing the applicability of engineered proteins in various fields.
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