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Mapping Dysfunctional Protein-Protein Interactions in Disease
Published on: October 24, 2025
959
Systematic protein-protein interaction mapping for clinically relevant human GPCRs
Kate Sokolina1, Saranya Kittanakom1, Jamie Snider1
1Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Molecular Systems Biology
|March 17, 2017
Summary
This study maps the human G-protein-coupled receptor (GPCR) interactome, identifying 686 interacting proteins. This provides a valuable resource for understanding GPCR signaling pathways and developing new therapeutics.
Area of Science:
- Integral membrane protein research
- Proteomics and interactomics
- Cellular signaling pathways
Background:
- G-protein-coupled receptors (GPCRs) are crucial integral membrane proteins regulating numerous signaling pathways.
- Their complex nature presents challenges for traditional proteomics studies.
- Understanding GPCR interactions is vital for drug discovery.
Purpose of the Study:
- To generate a global map of the human GPCR interactome.
- To identify novel components and pathways associated with GPCRs.
- To provide a resource for studying druggable GPCRs.
Main Methods:
- Utilized a modified membrane yeast two-hybrid (MYTH) approach.
- Investigated 48 full-length human ligand-unoccupied GPCRs in their native membrane environment.
- Identified interacting partners and mapped unique interactions.
Main Results:
- The study identified an interactome connecting 686 proteins via 987 unique interactions.
- Included 299 membrane proteins involved in diverse cellular functions.
- Validated novel interactions for GPR37, serotonin 5-HT4d, and adenosine ADORA2A receptors.
Conclusions:
- This work presents the first large-scale interactome map for human GPCRs.
- The GPCR interactome serves as a valuable resource for analyzing GPCR signaling.
- Facilitates the exploration of this druggable protein family for therapeutic targets.
Keywords:
G‐protein‐coupled receptorshigh‐throughput screeningintegrative computational biologyinteractomeprotein–protein interactionssplit‐ubiquitin membrane yeast two‐hybrid assayMore Related Videos
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