Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors
By S. Foster, Alexander Sebastian Hauser, Line Vedel, Ryan T. Strachan, Xi-Ping Huang, Ariana C. Gavin, Sushrut D Shah, A. Nayak, Linda M Haugaard-Kedström, R. Penn and 3 more. 2019
216 citations recorded by the source corpus.
Summary The peptidergic system is the most abundant network of ligand-receptor-mediated signaling in humans. However, the physiological roles remain elusive for numerous peptides and more than 100 G protein-coupled receptors (GPCRs). Here we report the pairing of cognate peptides and receptors. Integrating comparative genomics across 313 species and bioinformatics on all protein sequences and structures of human class A GPCRs, we identify universal characteristics that uncover additional potential peptidergic signaling systems. Using three orthogonal biochemical assays, we pair 17 proposed endogenous ligands with five orphan GPCRs that are associated with diseases, including genetic, neoplastic, nervous and reproductive system disorders. We also identify additional peptides for nine receptors with recognized ligands and pathophysiological roles. This integrated computational and multifaceted experimental approach expands the peptide-GPCR network and opens the way for studies to elucidate the roles of these signaling systems in human physiology and disease. Video Abstract
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Oncology
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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cellular and Molecular Neuroscience
- Albert J. Kooistra
- David E. Gloriam
- Gáspár Pándy-Szekeres
- Alibek Mamyrbekov
- György M. Keserü
- Christian Munk
- Stefan Mordalski
- Jimmy Caroli
In Molecular Biology
- Albert J. Kooistra
- Gáspár Pándy-Szekeres
- David E. Gloriam
- Alibek Mamyrbekov
- György M. Keserü
- Christian Munk
- Stefan Mordalski
- Mauricio Esguerra
Citations in the corpus
- GPCRdb in 2021: integrating GPCR sequence, structure and function (2020, background): “G protein-coupled receptors (GPCRs) account for 4% (799 (1) / 20 595 (2)) of human genes and mediate the actions of two-thirds (342/515) of hormones and neurotransmitters (3).”
- GPCRdb in 2023: state-specific structure models using AlphaFold2 and new ligand resources (2022, background): “G protein-coupled receptors (GPCRs) account for 799 (1) out of 20 383 (2) (4%) human genes and transduce the responses of two-thirds (342/515) of signaling substances (3).”