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Systematic protein–protein interaction mapping for clinically relevant human GPCR s
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Edité par CCSD ; EMBO Press -
International audience. G-protein-coupled receptors (GPCRs) are the largest family of integral membrane receptors with key roles in regulating signal-ing pathways targeted by therapeutics, but are difficult to study using existing proteomics technologies due to their complex biochemical features. To obtain a global view of GPCR-mediated signaling and to identify novel components of their pathways, we used a modified membrane yeast two-hybrid (MYTH) approach and identified interacting partners for 48 selected full-length human ligand-unoccupied GPCRs in their native membrane environment. The resulting GPCR interactome connects 686 proteins by 987 unique interactions, including 299 membrane proteins involved in a diverse range of cellular functions. To demonstrate the biological relevance of the GPCR inter-actome, we validated novel interactions of the GPR37, serotonin 5-HT4d, and adenosine ADORA2A receptors. Our data represent the first large-scale interactome mapping for human GPCRs and provide a valuable resource for the analysis of signaling pathways involving this druggable family of integral membrane proteins. Keywords G-protein-coupled receptors; high-throughput screening integrative computational biology; interactome; protein-protein interactions; split-ubiquitin membrane yeast two-hybrid assay
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