Common coupling map advances GPCR-G protein selectivity
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Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors that couple to G proteins to achieve appropriate functional responses. While G protein transducers from literature are annotated in the Guide to Pharmacology database, two recent large-scale datasets now expand the receptor-G protein 'couplome'. However, these three datasets differ in scope and reported G protein couplings giving different coverage and conclusions on G protein-coupled receptor (GPCR)-G protein signaling. Here, we report a common coupling map uncovering novel couplings supported by both large-scale studies, the selectivity/promiscuity of GPCRs and G proteins, and how the co-coupling and co-expression of G proteins compare to the families from phylogenetic relationships. The coupling map and insights on GPCR-G protein selectivity will catalyze advances in receptor research and cellular signaling toward the exploitation of G protein signaling bias in design of safer drugs.
Originalsprog | Engelsk |
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Artikelnummer | e74107 |
Tidsskrift | eLife |
Vol/bind | 11 |
Antal sider | 22 |
ISSN | 2050-084X |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Publisher Copyright:
© 2022, Hauser et al.
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