Common coupling map advances GPCR-G protein selectivity

Abstract
Data availability
Article and author information
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Abstract

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 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 towards the exploitation of G protein signaling bias in design of safer drugs.

Data availability

All underlying data are available in Spreadsheets S1-5. The obtained common coupling map is available in the online database GproteinDb at https://gproteindb.org/signprot/couplings.

The following previously published data sets were used

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https://doi.org/10.1093/nar/gkz951

Article and author information

Author details

Alexander Sebastian Hauser

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0003-1098-6419
Charlotte Avet

Department of Biochemistry and Molecular Medicine, University of Montreal, Montréal, Canada

Competing interests
No competing interests declared.
Claire Normand

Domain Therapeutics North America, Montréal, Canada

Competing interests
Claire Normand, was an employees of Domain Therapeutics North America during part or all of this research..
Arturo Mancini

Domain Therapeutics North America, Montréal, Canada

Competing interests
Arturo Mancini, was an employees of Domain Therapeutics North America during part or all of this research..
Asuka Inoue

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

Competing interests
No competing interests declared.
Michel Bouvier

Department of Biochemistry and Molecular Medicine, University of Montreal, Montréal, Canada

For correspondence
michel.bouvier@umontreal.ca

Competing interests
Michel Bouvier, is the president of Domain Therapeutics scientific advisory board..

"This ORCID iD identifies the author of this article:" 0000-0003-1128-0100
David E Gloriam

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

For correspondence
david.gloriam@sund.ku.dk

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4299-7561

Funding

Canadian Institutes of Health Research (FDN-148431)

Michel Bouvier

Lundbeckfonden (R218-2016-1266)

David E Gloriam

Lundbeckfonden (R313-2019-526)

David E Gloriam

Novo Nordisk Fonden (NNF18OC0031226)

David E Gloriam

Basis for Supporting Innovative Drug Discovery and Life Science Research (JP20am0101095)

Asuka Inoue

Leading Asia's Private Infrastructure Fund (JP20gm0010004)

Asuka Inoue

Japan Agency for Medical Research and Development

Asuka Inoue

Takeda Science Foundation

Asuka Inoue

Uehara Memorial Foundation

Asuka Inoue

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.