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Systematic identification of phosphorylation-mediated protein interaction switches
Matthew J Betts1,2, Oliver Wichmann1,2, Mathias Utz1,2
1CellNetworks, Bioquant, University of Heidelberg, Im Neuenheimer Feld 267, Heidelberg, Germany.
Plos Computational Biology
|March 28, 2017
Summary
This study introduces a rapid method to predict phosphorylation switches, which regulate protein interactions. Researchers identified over a thousand potential switches, suggesting this is a common ancient mechanism in kinase phosphorylation.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Proteomics identifies numerous phosphorylation sites, but their functions are often unknown.
- Understanding the role of phosphorylation in regulating protein interactions is crucial.
Purpose of the Study:
- To develop a fast method for predicting phosphorylation-mediated switches.
- To identify potential phosphorylation sites that modulate protein-protein interactions.
Main Methods:
- Mapping identified phosphorylation sites to known protein-protein interaction structures.
- Analyzing the properties of protein interfaces at phosphorylation sites.
- Predicting phosphorylation sites that could enable or disable interactions.
Main Results:
- Successfully predicted 1024 potential phosphorylation switches.
- Experimental validation confirmed that phosphomimetic mutations impact protein interactions.
- Identified phosphorylation sites on globular proteins as frequent interaction switches.
Conclusions:
- Phosphorylation frequently acts as a switch to regulate protein interactions, particularly on structured protein regions.
- Thousands of such phosphorylation-mediated switches remain undiscovered in existing datasets.
- This mechanism may represent an ancient role of kinase-mediated phosphorylation.
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