Open AccessSystematic protein–protein interaction mapping for clinically relevant human GPCR s
Author(s) -
Sokolina Kate,
Kittanakom Saranya,
Snider Jamie,
Kotlyar Max,
Maurice Pascal,
Gandía Jorge,
BenleulmiChaachoua Abla,
Tadagaki Kenjiro,
Oishi Atsuro,
Wong Victoria,
Malty Ramy H,
Deineko Viktor,
Aoki Hiroyuki,
Amin Shahreen,
Yao Zhong,
Morató Xavier,
Otasek David,
Kobayashi Hiroyuki,
Menendez Javier,
Auerbach Daniel,
Angers Stephane,
Pržulj Natasa,
Bouvier Michel,
Babu Mohan,
Ciruela Francisco,
Jockers Ralf,
Jurisica Igor,
Stagljar Igor
Publication year - 2017
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20167430
Subject(s) - interactome , g protein coupled receptor , biology , druggability , computational biology , integral membrane protein , membrane protein , proteomics , protein–protein interaction , signal transduction , microbiology and biotechnology , biochemistry , membrane , gene
G‐protein‐coupled receptors ( GPCR s) are the largest family of integral membrane receptors with key roles in regulating signaling 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 GPCR s 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 interactome, we validated novel interactions of the GPR 37, serotonin 5‐ HT 4d, and adenosine ADORA 2A receptors. Our data represent the first large‐scale interactome mapping for human GPCR s and provide a valuable resource for the analysis of signaling pathways involving this druggable family of integral membrane proteins.