Common coupling map advances GPCR-G protein selectivity.

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. © 2022, Hauser et al.

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Alexander S Hauser, Charlotte Avet, Claire Normand, Arturo Mancini, Asuka Inoue, Michel Bouvier, David E Gloriam. Common coupling map advances GPCR-G protein selectivity. eLife. 2022 Mar 18;11

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PMID: 35302494

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