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CoDIAC: A comprehensive approach for interaction analysis reveals novel insights into SH2 domain function and
Alekhya Kandoor1, Gabrielle Martinez1, Julianna M Hitchcock1
1Department of Biomedical Engineering and the Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.
Biorxiv : the Preprint Server for Biology
|August 2, 2024
Summary
We developed a new method to map protein domain interactions and analyzed the human SH2 domain family. This revealed conserved regulation of signaling pathways by post-translational modifications.
Area of Science:
- Biochemistry
- Structural Biology
- Bioinformatics
Background:
- Protein domains are fundamental units of protein structure and function.
- Evolutionary processes lead to diverse domain arrangements and specificities.
- Understanding domain interactions is crucial for deciphering cellular signaling.
Purpose of the Study:
- To develop a structure-based method for comprehensive mapping of protein domain interfaces.
- To investigate domain-ligand interactions, conservation of domain-domain interfaces, and post-translational modification sites.
- To apply this approach to the human SH2 domain family to understand phosphotyrosine signaling.
Main Methods:
- Developed a structure-based interface analysis to map domain interfaces from experimental and predicted structures.
- Applied contact mapping to analyze domain selectivity, interface conservation, and post-translational modification regions.
- Utilized the human SH2 domain family as a model system.
Main Results:
- Identified novel insights into SH2 domain binding selectivity.
- Found evidence for coordinated and conserved regulation of SH2 domain interfaces by phosphorylation and acetylation.
- Demonstrated that multiple signaling systems can regulate protein activity and SH2 domain interactions.
Conclusions:
- The developed method provides a comprehensive approach to analyzing domain interfaces.
- The study reveals complex regulatory mechanisms within the SH2 domain family and phosphotyrosine signaling.
- An open-source Python package, CoDIAC, is provided for domain interface analysis.
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