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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...

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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
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author Hauser, Alexander S
Avet, Charlotte
Normand, Claire
Mancini, Arturo
Inoue, Asuka
Bouvier, Michel
Gloriam, David E
author_facet Hauser, Alexander S
Avet, Charlotte
Normand, Claire
Mancini, Arturo
Inoue, Asuka
Bouvier, Michel
Gloriam, David E
author_sort Hauser, Alexander S
collection PubMed
description 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.
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spelling pubmed-90051892022-04-13 Common coupling map advances GPCR-G protein selectivity Hauser, Alexander S Avet, Charlotte Normand, Claire Mancini, Arturo Inoue, Asuka Bouvier, Michel Gloriam, David E eLife Computational and Systems Biology 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. eLife Sciences Publications, Ltd 2022-03-18 /pmc/articles/PMC9005189/ /pubmed/35302494 http://dx.doi.org/10.7554/eLife.74107 Text en © 2022, Hauser et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Hauser, Alexander S
Avet, Charlotte
Normand, Claire
Mancini, Arturo
Inoue, Asuka
Bouvier, Michel
Gloriam, David E
Common coupling map advances GPCR-G protein selectivity
title Common coupling map advances GPCR-G protein selectivity
title_full Common coupling map advances GPCR-G protein selectivity
title_fullStr Common coupling map advances GPCR-G protein selectivity
title_full_unstemmed Common coupling map advances GPCR-G protein selectivity
title_short Common coupling map advances GPCR-G protein selectivity
title_sort common coupling map advances gpcr-g protein selectivity
topic Computational and Systems Biology
url 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
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