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Published on: March 7, 2019
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The relationship between interfacial overlap and functional divergence in the yeast protein-protein interaction
Yilun Han1, Mohamed Ghadie2, Yu Xia1
1Department of Bioengineering, McGill University, Montreal, QC H3A 0E9, Canada.
Structure (London, England : 1993)
|September 18, 2025
Summary
Protein binding interfaces and protein functions are linked. Proteins sharing binding sites on a target protein tend to have different functions, suggesting competitive binding drives functional divergence.
Area of Science:
- Molecular Biology
- Systems Biology
- Structural Biology
Background:
- Protein-protein interactions (PPIs) are fundamental to cellular processes.
- Understanding the link between protein structure and function is a key biological challenge.
- Genetic interactions provide insights into functional relationships between proteins.
Purpose of the Study:
- To investigate the relationship between structural divergence of protein-protein interactions (PPIs) and functional divergence.
- To explore how shared binding interfaces influence protein function.
- To determine if competitive binding explains functional divergence in protein interaction networks.
Main Methods:
- Analysis of a structurally resolved yeast PPI network.
- Quantification of PPI structural divergence using interfacial overlap.
- Measurement of functional divergence using genetic interaction profile similarity.
Main Results:
- A significant negative correlation was found between interfacial overlap and genetic interaction profile similarity.
- Interactor pairs with high interfacial overlap exhibited divergent phenotypic-level functions.
- The correlation was strongest when using genetic interaction profiles for functional similarity measurement.
Conclusions:
- Competitive binding appears to be a key driver of functional divergence in proteins.
- Structural constraints on binding interfaces can lead to functional specialization.
- The study highlights the interplay between structural and functional aspects of protein interactions.
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