Rules and mechanisms governing G protein coupling selectivity of GPCRs
Summary: G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: Gi/o, Gq, Gs, and G12/13. However, our understanding of the G protein selectivity of GPCRs is incomplete. Here, we quantitatively measure...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723011853 |
| _version_ | 1797676304998334464 |
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| author | Ikuo Masuho Ryoji Kise Pablo Gainza Ee Von Moo Xiaona Li Ryosuke Tany Hideko Wakasugi-Masuho Bruno E. Correia Kirill A. Martemyanov |
| author_facet | Ikuo Masuho Ryoji Kise Pablo Gainza Ee Von Moo Xiaona Li Ryosuke Tany Hideko Wakasugi-Masuho Bruno E. Correia Kirill A. Martemyanov |
| author_sort | Ikuo Masuho |
| collection | DOAJ |
| description | Summary: G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: Gi/o, Gq, Gs, and G12/13. However, our understanding of the G protein selectivity of GPCRs is incomplete. Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. We further identify the structural determinants of G protein selectivity, allowing us to synthesize non-existent GPCRs with de novo G protein selectivity and efficiently identify putative pathogenic variants. |
| first_indexed | 2024-03-11T22:27:03Z |
| format | Article |
| id | doaj.art-9dcef49af9894a03b9baf4ad1e758c40 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T22:27:03Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9dcef49af9894a03b9baf4ad1e758c402023-09-24T05:15:04ZengElsevierCell Reports2211-12472023-10-014210113173Rules and mechanisms governing G protein coupling selectivity of GPCRsIkuo Masuho0Ryoji Kise1Pablo Gainza2Ee Von Moo3Xiaona Li4Ryosuke Tany5Hideko Wakasugi-Masuho6Bruno E. Correia7Kirill A. Martemyanov8Department of Neuroscience, UF Scripps Biomedical Research, Jupiter, FL 33458, USA; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USA; Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA; Corresponding authorPediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USALaboratory of Protein Design and Immunoengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, SwitzerlandDepartment of Neuroscience, UF Scripps Biomedical Research, Jupiter, FL 33458, USADepartment of Neuroscience, UF Scripps Biomedical Research, Jupiter, FL 33458, USAPediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USADepartment of Neuroscience, UF Scripps Biomedical Research, Jupiter, FL 33458, USA; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USALaboratory of Protein Design and Immunoengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, SwitzerlandDepartment of Neuroscience, UF Scripps Biomedical Research, Jupiter, FL 33458, USA; Corresponding authorSummary: G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: Gi/o, Gq, Gs, and G12/13. However, our understanding of the G protein selectivity of GPCRs is incomplete. Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. We further identify the structural determinants of G protein selectivity, allowing us to synthesize non-existent GPCRs with de novo G protein selectivity and efficiently identify putative pathogenic variants.http://www.sciencedirect.com/science/article/pii/S2211124723011853CP: Cell biology |
| spellingShingle | Ikuo Masuho Ryoji Kise Pablo Gainza Ee Von Moo Xiaona Li Ryosuke Tany Hideko Wakasugi-Masuho Bruno E. Correia Kirill A. Martemyanov Rules and mechanisms governing G protein coupling selectivity of GPCRs Cell Reports CP: Cell biology |
| title | Rules and mechanisms governing G protein coupling selectivity of GPCRs |
| title_full | Rules and mechanisms governing G protein coupling selectivity of GPCRs |
| title_fullStr | Rules and mechanisms governing G protein coupling selectivity of GPCRs |
| title_full_unstemmed | Rules and mechanisms governing G protein coupling selectivity of GPCRs |
| title_short | Rules and mechanisms governing G protein coupling selectivity of GPCRs |
| title_sort | rules and mechanisms governing g protein coupling selectivity of gpcrs |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723011853 |
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