Molecular Systems Biology (Mar 2017)
Systematic protein–protein interaction mapping for clinically relevant human GPCRs
- Kate Sokolina,
- Saranya Kittanakom,
- Jamie Snider,
- Max Kotlyar,
- Pascal Maurice,
- Jorge Gandía,
- Abla Benleulmi‐Chaachoua,
- Kenjiro Tadagaki,
- Atsuro Oishi,
- Victoria Wong,
- Ramy H Malty,
- Viktor Deineko,
- Hiroyuki Aoki,
- Shahreen Amin,
- Zhong Yao,
- Xavier Morató,
- David Otasek,
- Hiroyuki Kobayashi,
- Javier Menendez,
- Daniel Auerbach,
- Stephane Angers,
- Natasa Pržulj,
- Michel Bouvier,
- Mohan Babu,
- Francisco Ciruela,
- Ralf Jockers,
- Igor Jurisica,
- Igor Stagljar
Affiliations
- Kate Sokolina
- Donnelly Centre University of Toronto Toronto ON Canada
- Saranya Kittanakom
- Donnelly Centre University of Toronto Toronto ON Canada
- Jamie Snider
- Donnelly Centre University of Toronto Toronto ON Canada
- Max Kotlyar
- Princess Margaret Cancer Centre University Health Network University of Toronto Toronto ON Canada
- Pascal Maurice
- Inserm, U1016 Institut Cochin Paris France
- Jorge Gandía
- Unitat de Farmacologia Departament de Patologia i Terapèutica Experimental Facultat de Medicina IDIBELL Universitat de Barcelona L'Hospitalet de Llobregat Barcelona Spain
- Abla Benleulmi‐Chaachoua
- Inserm, U1016 Institut Cochin Paris France
- Kenjiro Tadagaki
- Inserm, U1016 Institut Cochin Paris France
- Atsuro Oishi
- Inserm, U1016 Institut Cochin Paris France
- Victoria Wong
- Donnelly Centre University of Toronto Toronto ON Canada
- Ramy H Malty
- Department of Biochemistry Research and Innovation Centre University of Regina Regina SK Canada
- Viktor Deineko
- Department of Biochemistry Research and Innovation Centre University of Regina Regina SK Canada
- Hiroyuki Aoki
- Department of Biochemistry Research and Innovation Centre University of Regina Regina SK Canada
- Shahreen Amin
- Department of Biochemistry Research and Innovation Centre University of Regina Regina SK Canada
- Zhong Yao
- Donnelly Centre University of Toronto Toronto ON Canada
- Xavier Morató
- Unitat de Farmacologia Departament de Patologia i Terapèutica Experimental Facultat de Medicina IDIBELL Universitat de Barcelona L'Hospitalet de Llobregat Barcelona Spain
- David Otasek
- Princess Margaret Cancer Centre University Health Network University of Toronto Toronto ON Canada
- Hiroyuki Kobayashi
- Department of Biochemistry Institute for Research in Immunology & Cancer Université de Montréal Montréal QC Canada
- Javier Menendez
- Donnelly Centre University of Toronto Toronto ON Canada
- Daniel Auerbach
- Dualsystems Biotech AG Schlieren Switzerland
- Stephane Angers
- Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy and Department of Biochemistry Faculty of Medicine University of Toronto Toronto ON Canada
- Natasa Pržulj
- Department of Computing University College London London UK
- Michel Bouvier
- Department of Biochemistry Institute for Research in Immunology & Cancer Université de Montréal Montréal QC Canada
- Mohan Babu
- Department of Biochemistry Research and Innovation Centre University of Regina Regina SK Canada
- Francisco Ciruela
- Unitat de Farmacologia Departament de Patologia i Terapèutica Experimental Facultat de Medicina IDIBELL Universitat de Barcelona L'Hospitalet de Llobregat Barcelona Spain
- Ralf Jockers
- Inserm, U1016 Institut Cochin Paris France
- Igor Jurisica
- Princess Margaret Cancer Centre University Health Network University of Toronto Toronto ON Canada
- Igor Stagljar
- Donnelly Centre University of Toronto Toronto ON Canada
- DOI
- https://doi.org/10.15252/msb.20167430
- Journal volume & issue
-
Vol. 13,
no. 3
pp. n/a – n/a
Abstract
Abstract G‐protein‐coupled receptors (GPCRs) 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 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 interactome, 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