The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Illuminating G-Protein-Coupling Selectivity of GPCRs
Open accessAbstract
SUMMARY Heterotrimetic G proteins consist of four subfamilies (GS, Gi/O, Gq/11, and G12/13) that mediate signaling via G-protein-coupled receptors (GPCRs), principally by receptors binding Gα C termini. G-protein-coupling profiles govern GPCR-induced cellular responses, yet receptor sequence selectivity determinants remain elusive. Here, we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique Gα subunit C termini. For each receptor, we probed chimeric Gα subunit activation via a transforming growth factor-α (TGF-α) shedding response in HEK293 cells lacking endogenous Gq/11 and G12/13 proteins, and complemented G-protein-coupling profiles through a NanoBiT-G-protein dissociation assay. Interrogation of the dataset identified sequence-based coupling specificity features, inside and outside the transmembrane domain, which we used to develop a coupling predictor that outperforms previous methods. We used the predictor to engineer designer GPCRs selectively coupled to G12. This dataset of fine-tuned signaling mechanisms for diverse GPCRs is a valuable resource for research in GPCR signaling.
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Metadata
- Authors
- Inoue, A., Raimondi, F., Kadji, F. M. N., Singh, G., Kishi, T., Uwamizu, A., Ono, Y., Shinjo, Y., Ishida, S., Arang, N., Kawakami, K., Gutkind, J. S., Aoki, J., & Russell, R. B.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 177
- Issue
- 7
- Pages
- 1933-1947.e25
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2946861851
- Cited by
- 638
- References
- 6
- FWCI
- 18.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Inoue, A., Raimondi, F., Kadji, F. M. N., Singh, G., Kishi, T., Uwamizu, A., Ono, Y., Shinjo, Y., Ishida, S., Arang, N., Kawakami, K., Gutkind, J. S., Aoki, J., & Russell, R. B. (2019). Illuminating G-Protein-Coupling Selectivity of GPCRs. Cell. https://doi.org/10.1016/j.cell.2019.04.044
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