Systematic protein–protein interaction mapping for clinically relevant human GPCRs
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2017-03-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20167430 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594350709669888 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Kate Sokolina |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8967c8058cf7455eb51b7bdd45452e18 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-8967c8058cf7455eb51b7bdd45452e182025-01-19T12:44:11ZengSpringer NatureMolecular Systems Biology1744-42922017-03-0113311910.15252/msb.20167430Systematic protein–protein interaction mapping for clinically relevant human GPCRsKate Sokolina0Saranya Kittanakom1Jamie Snider2Max Kotlyar3Pascal Maurice4Jorge Gandía5Abla Benleulmi‐Chaachoua6Kenjiro Tadagaki7Atsuro Oishi8Victoria Wong9Ramy H Malty10Viktor Deineko11Hiroyuki Aoki12Shahreen Amin13Zhong Yao14Xavier Morató15David Otasek16Hiroyuki Kobayashi17Javier Menendez18Daniel Auerbach19Stephane Angers20Natasa Pržulj21Michel Bouvier22Mohan Babu23Francisco Ciruela24Ralf Jockers25Igor Jurisica26Igor Stagljar27Donnelly Centre, University of TorontoDonnelly Centre, University of TorontoDonnelly Centre, University of TorontoPrincess Margaret Cancer Centre, University Health Network, University of TorontoInserm, U1016, Institut CochinUnitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L'Hospitalet de LlobregatInserm, U1016, Institut CochinInserm, U1016, Institut CochinInserm, U1016, Institut CochinDonnelly Centre, University of TorontoDepartment of Biochemistry, Research and Innovation Centre, University of ReginaDepartment of Biochemistry, Research and Innovation Centre, University of ReginaDepartment of Biochemistry, Research and Innovation Centre, University of ReginaDepartment of Biochemistry, Research and Innovation Centre, University of ReginaDonnelly Centre, University of TorontoUnitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L'Hospitalet de LlobregatPrincess Margaret Cancer Centre, University Health Network, University of TorontoDepartment of Biochemistry, Institute for Research in Immunology & Cancer, Université de MontréalDonnelly Centre, University of TorontoDualsystems Biotech AGDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy and Department of Biochemistry, Faculty of Medicine, University of TorontoDepartment of Computing, University College LondonDepartment of Biochemistry, Institute for Research in Immunology & Cancer, Université de MontréalDepartment of Biochemistry, Research and Innovation Centre, University of ReginaUnitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L'Hospitalet de LlobregatInserm, U1016, Institut CochinPrincess Margaret Cancer Centre, University Health Network, University of TorontoDonnelly Centre, University of TorontoAbstract 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.https://doi.org/10.15252/msb.20167430G‐protein‐coupled receptorshigh‐throughput screeningintegrative computational biologyinteractomeprotein–protein interactionssplit‐ubiquitin membrane yeast two‐hybrid assay |
| spellingShingle | 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 Systematic protein–protein interaction mapping for clinically relevant human GPCRs Molecular Systems Biology G‐protein‐coupled receptors high‐throughput screening integrative computational biology interactome protein–protein interactions split‐ubiquitin membrane yeast two‐hybrid assay |
| title | Systematic protein–protein interaction mapping for clinically relevant human GPCRs |
| title_full | Systematic protein–protein interaction mapping for clinically relevant human GPCRs |
| title_fullStr | Systematic protein–protein interaction mapping for clinically relevant human GPCRs |
| title_full_unstemmed | Systematic protein–protein interaction mapping for clinically relevant human GPCRs |
| title_short | Systematic protein–protein interaction mapping for clinically relevant human GPCRs |
| title_sort | systematic protein protein interaction mapping for clinically relevant human gpcrs |
| topic | G‐protein‐coupled receptors high‐throughput screening integrative computational biology interactome protein–protein interactions split‐ubiquitin membrane yeast two‐hybrid assay |
| url | https://doi.org/10.15252/msb.20167430 |
| work_keys_str_mv | AT katesokolina systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT saranyakittanakom systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT jamiesnider systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT maxkotlyar systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT pascalmaurice systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT jorgegandia systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT ablabenleulmichaachoua systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT kenjirotadagaki systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT atsurooishi systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT victoriawong systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT ramyhmalty systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT viktordeineko systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT hiroyukiaoki systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT shahreenamin systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT zhongyao systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT xaviermorato systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT davidotasek systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT hiroyukikobayashi systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT javiermenendez systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT danielauerbach systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT stephaneangers systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT natasaprzulj systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT michelbouvier systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT mohanbabu systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT franciscociruela systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT ralfjockers systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT igorjurisica systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs AT igorstagljar systematicproteinproteininteractionmappingforclinicallyrelevanthumangpcrs |