Common coupling map advances GPCR-G protein selectivity

  1. Alexander Sebastian Hauser
  2. Charlotte Avet
  3. Claire Normand
  4. Arturo Mancini
  5. Asuka Inoue
  6. Michel Bouvier  Is a corresponding author
  7. David E Gloriam  Is a corresponding author
  1. University of Copenhagen, Denmark
  2. University of Montreal, Canada
  3. Domain Therapeutics North America, Canada
  4. Tohoku University, Japan

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

Article and author information

Author details

  1. Alexander Sebastian Hauser

    Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1098-6419
  2. Charlotte Avet

    Department of Biochemistry and Molecular Medicine, University of Montreal, Montréal, Canada
    Competing interests
    No competing interests declared.
  3. 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..
  4. 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..
  5. Asuka Inoue

    Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    Competing interests
    No competing interests declared.
  6. 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..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1128-0100
  7. 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.
    ORCID icon "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.

Reviewing Editor

  1. William I Weis, Stanford University School of Medicine, United States

Publication history

  1. Preprint posted: September 8, 2021 (view preprint)
  2. Received: September 21, 2021
  3. Accepted: March 17, 2022
  4. Accepted Manuscript published: March 18, 2022 (version 1)
  5. Version of Record published: April 12, 2022 (version 2)

Copyright

© 2022, Hauser et al.

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.

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  1. Alexander Sebastian Hauser
  2. Charlotte Avet
  3. Claire Normand
  4. Arturo Mancini
  5. Asuka Inoue
  6. Michel Bouvier
  7. David E Gloriam
(2022)
Common coupling map advances GPCR-G protein selectivity
eLife 11:e74107.
https://doi.org/10.7554/eLife.74107

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