TY - JOUR

T1 - Common coupling map advances GPCR-G protein selectivity

AU - Hauser, Alexander S.

AU - Avet, Charlotte

AU - Normand, Claire

AU - Mancini, Arturo

AU - Inoue, Asuka

AU - Bouvier, Michel

AU - Gloriam, David E.

N1 - Publisher Copyright: © 2022, Hauser et al.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - computational biology

KW - G protein

KW - GPCR

KW - human

KW - pharmacology

KW - signal transduction

KW - systems biology

U2 - 10.7554/eLife.74107

DO - 10.7554/eLife.74107

M3 - Journal article

C2 - 35302494

AN - SCOPUS:85128489166

VL - 11

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e74107

ER -