| + |
DRD1 | up-regulates activity 
binding
|
GNAS |
0.518 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282053 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281582 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31142646 |
Here, we directly assess coupling between 14 representative GPCRs and 16 Gα subunits, including one wild-type Gα subunit from each of the four families and 12 chimeras with exchanged C termini. We use a sensitive bioluminescence resonance energy transfer (BRET) assay that provides control over both ligand and nucleotide binding, and allows direct comparison across G protein families. We find that the Gs- and Gq-coupled receptors we studied are relatively promiscuous and always couple to some extent to Gi1 heterotrimers. In contrast, Gi-coupled receptors are more selective. Our results with Gα subunit chimeras show that the Gα C terminus is important for coupling selectivity, but no more so than the Gα subunit core. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256796 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282210 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 37742189 |
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. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
DRD1 | up-regulates activity
binding
|
GNAZ |
0.265 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257269 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281770 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
DRD1 | up-regulates activity
binding
|
GNAI3 |
0.278 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257181 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DRD1 | up-regulates activity
binding
|
GNA14 |
0.261 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257391 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DRD1 | up-regulates activity
binding
|
GNAQ |
0.513 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257335 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Dopaminergic Synapse |
| + |
DRD1 | up-regulates activity
binding
|
GNAO1 |
0.34 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281771 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DRD1 | up-regulates activity
binding
|
GNA15 |
0.339 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282127 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282393 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 37742189 |
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. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
dopamine | up-regulates activity
chemical activation
|
DRD1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257477 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Dopaminergic Synapse |
| + |
DRD1 | up-regulates activity
binding
|
GNAI1 |
0.28 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257068 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281581 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31142646 |
Here, we directly assess coupling between 14 representative GPCRs and 16 Gα subunits, including one wild-type Gα subunit from each of the four families and 12 chimeras with exchanged C termini. We use a sensitive bioluminescence resonance energy transfer (BRET) assay that provides control over both ligand and nucleotide binding, and allows direct comparison across G protein families. We find that the Gs- and Gq-coupled receptors we studied are relatively promiscuous and always couple to some extent to Gi1 heterotrimers. In contrast, Gi-coupled receptors are more selective. Our results with Gα subunit chimeras show that the Gα C terminus is important for coupling selectivity, but no more so than the Gα subunit core. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
DRD1 | up-regulates activity
binding
|
GNAL |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256939 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Dopaminergic Synapse |
4.0
DRD1
- 
- 