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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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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. |
format | Online Article Text |
id | pubmed-9005189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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