Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Discovery of Human Signaling Systems : Pairing Peptides to G Protein-Coupled Receptors. / Foster, Simon R; Hauser, Alexander S; Vedel, Line; Strachan, Ryan T; Huang, Xi-Ping; Gavin, Ariana C; Shah, Sushrut D; Nayak, Ajay P; Haugaard-Kedström, Linda M; Penn, Raymond B; Roth, Bryan L; Bräuner-Osborne, Hans; Gloriam, David E.
I: Cell, Bind 179, Nr. 4, 31.10.2019, s. 895-908.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Discovery of Human Signaling Systems
T2 - Pairing Peptides to G Protein-Coupled Receptors
AU - Foster, Simon R
AU - Hauser, Alexander S
AU - Vedel, Line
AU - Strachan, Ryan T
AU - Huang, Xi-Ping
AU - Gavin, Ariana C
AU - Shah, Sushrut D
AU - Nayak, Ajay P
AU - Haugaard-Kedström, Linda M
AU - Penn, Raymond B
AU - Roth, Bryan L
AU - Bräuner-Osborne, Hans
AU - Gloriam, David E
N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2019/10/31
Y1 - 2019/10/31
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2019.10.010
DO - 10.1016/j.cell.2019.10.010
M3 - Journal article
C2 - 31675498
VL - 179
SP - 895
EP - 908
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -
ID: 229778288