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Updated: Feb 27, 2026
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A Novel Saturation Mutagenesis Approach: Single Step Characterization of Regulatory Protein Binding Sites in RNA Using Phosphorothioates
Published on: August 21, 2018
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Deconstruction of the Ras switching cycle through saturation mutagenesis
Pradeep Bandaru1,2,3, Neel H Shah1,2,3, Moitrayee Bhattacharyya1,2,3
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Elife
|July 8, 2017
Summary
Ras proteins are highly conserved due to their regulators. Removing these regulators reveals mutations that promote the inactive state, explaining Ras sequence conservation in its biochemical network.
Area of Science:
- Molecular Biology
- Biochemistry
- Evolutionary Biology
Background:
- Ras proteins are crucial signaling molecules with conserved sequences, switching between active and inactive states.
- Understanding Ras sequence conservation is vital, especially given general protein mutational tolerance.
Purpose of the Study:
- To investigate the mechanistic basis for Ras sequence conservation.
- To identify constraints on Ras sequence through mutational analysis.
Main Methods:
- Deep mutational scanning
- Biochemical analysis
- Molecular simulations
- Evolutionary analysis
Main Results:
- Ras exhibits global sensitivity to mutation when interacting with GTPase activating protein and nucleotide exchange factor.
- Removing regulators reveals largely neutral mutational effects and identifies hotspots for activating mutations.
- Evolutionary analysis suggests co-evolution of Ras and its regulators in vertebrates.
Conclusions:
- Ras sequence conservation is strongly dependent on its biochemical network and interactions.
- This study provides a framework for understanding global selection pressures on proteins like Ras.
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