Affiliation:
1. Department of Drug Design and Pharmacology, University of Copenhagen
2. Institute for Research in Immunology and Cancer (IRIC), and Department of Biochemistry and Molecular Medicine, Université de Montréal
3. Domain Therapeutics North America
4. Graduate School of Pharmaceutical Sciences, Tohoku University
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 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.
Funder
Canadian Institutes of Health Research
Lundbeckfonden
Novo Nordisk Fonden
Japan Agency for Medical Research and Development
Takeda Science Foundation
Uehara Memorial Foundation
Japan Society for the Promotion of Science
Japan Science and Technology Agency
Daiichi Sankyo Foundation of Life Science
Independent Research Fund Denmark
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
54 articles.
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