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Entropic stabilization of proteins and its proteomic consequences
Igor N Berezovsky1, William W Chen, Paul J Choi
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America.
Plos Computational Biology
|October 5, 2005
Summary
Evolutionary adaptation to heat involves specific amino acid changes. Lysine
Area of Science:
- Biophysics
- Genomics
- Protein Evolution
Background:
- Thermophilic adaptation is observed in whole-genome compositional biases.
- The physical mechanisms behind protein thermal stabilization are not fully understood.
- Hyperthermophiles have more charged residues, particularly lysines over arginines.
Purpose of the Study:
- Investigate the role of amino acid composition in thermophilic adaptation.
- Explore the physical mechanisms of protein thermal stabilization.
- Resolve the puzzle of lysine enrichment over arginine in hyperthermophiles.
Main Methods:
- All-atom simulations to analyze amino acid rotamers and stability.
- Computational experiments on arginine-to-lysine substitutions.
- High-throughput comparative analysis of complete proteomes.
Main Results:
- Lysines possess more accessible rotamers than arginines, suggesting entropic stabilization.
- Arginine-to-lysine substitutions enhance protein stability.
- Hyperthermophiles show a strong bias toward lysine over arginine, not explained by GC content or general amino acid trends.
Conclusions:
- A novel entropic mechanism of protein thermostability, driven by rotamer isomerization dynamics, has been identified.
- This mechanism explains the preferential enrichment of lysines over arginines in hyperthermophilic proteomes.
- Understanding physical mechanisms aids in resolving comparative genomics puzzles regarding protein evolution.