Cargando…

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 th...

Descripción completa

Detalles Bibliográficos
Autores principales: Hauser, Alexander S, Avet, Charlotte, Normand, Claire, Mancini, Arturo, Inoue, Asuka, Bouvier, Michel, Gloriam, David E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005189/
https://www.ncbi.nlm.nih.gov/pubmed/35302494
http://dx.doi.org/10.7554/eLife.74107
Descripción
Sumario: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.