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Published on: August 18, 2023
Stability effects of mutations and protein evolvability.
Nobuhiko Tokuriki1, Dan S Tawfik
1Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Current Opinion in Structural Biology
|September 22, 2009
Summary
Protein mutations can destabilize proteins, limiting their ability to evolve new functions. Understanding and overcoming these stability constraints is key to protein evolvability in nature and the lab.
Area of Science:
- Protein Biophysics
- Molecular Evolution
- Biochemistry
Background:
- The traditional view held that proteins tolerate most amino acid substitutions.
- Emerging evidence highlights mutation-induced instability as a key constraint on protein evolvability.
- Protein stability (thermodynamic and kinetic) is crucial for function and evolution.
Purpose of the Study:
- To review recent findings on mutation effects on protein stability.
- To explore the relationship between protein stability and evolution.
- To discuss methods for predicting stability changes and compensatory mechanisms.
Main Methods:
- Literature review of recent research in protein biophysics and evolution.
- Analysis of mutation effects on protein thermodynamic and kinetic stability.
- Examination of mechanisms that buffer or compensate for destabilizing mutations.
Main Results:
- Mutations frequently have deleterious effects on protein stability.
- Protein stability significantly constrains protein evolvability.
- Predictive methods and compensatory mechanisms can overcome stability limitations.
Conclusions:
- Protein stability is a critical factor limiting evolutionary trajectories.
- Understanding stability effects allows for prediction and engineering of protein evolvability.
- Compensatory mechanisms play a vital role in enabling protein adaptation.
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