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Updated: Jul 13, 2026
08:59
Analysis of Protein Folding, Transport, and Degradation in Living Cells by Radioactive Pulse Chase
Published on: February 12, 2019
Evolution of a protein fold in vitro
M H Cordes1, N P Walsh, C J McKnight
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|April 9, 1999
Summary
Protein engineering reveals that minor mutations can significantly alter protein structure. A "switch" mutant of the Arc repressor demonstrated that small genetic changes can lead to novel protein folds without extensive mutagenesis.
Area of Science:
- Protein Engineering
- Structural Biology
- Molecular Evolution
Background:
- The Arc repressor is a transcriptional regulator.
- Understanding protein folding and evolution is crucial for protein design.
- Mutagenesis studies explore structure-function relationships.
Purpose of the Study:
- To investigate the structural consequences of specific mutations in the Arc repressor.
- To explore the potential for evolving new protein folds through targeted mutagenesis.
Main Methods:
- Construction of a "switch" mutant by interchanging leucine 12 and asparagine 11 residues.
- Analysis of the mutant protein's fold and side-chain packing.
- Utilizing structural biology techniques to observe conformational changes.
Main Results:
- The mutant protein adopted a helical fold, replacing the original beta sheet structure.
- Significant repacking of side chains occurred in the altered region.
- The structural changes successfully maintained optimal hydrophobic core burial and polar group solvent exposure.
Conclusions:
- Minor, targeted mutagenesis can induce significant changes in protein fold.
- Evolution of new protein folds may occur through incremental alterations rather than large-scale changes.
- This study provides insights into the plasticity of protein structures and their evolutionary potential.
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