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Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors

Cell. 2019; 
Foster SR, Hauser AS, Vedel L, Strachan RT, Huang XP, Gavin AC, Shah SD, Nayak AP, Haugaard-Kedström LM, Penn RB, Roth BL, Bräuner-Osborne H, Gloriam DE
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Peptide Synthesis Peptides were purchased as a custom designed peptide library from Genscript, with > 95% purity cutoff and delivered as lyophilized acetate salts. In total, the library included 219 peptides varying in length from 3 – 50 amino acids, (full details and quality control data are found in Table S4).  Get A Quote

摘要

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 reproduct... More

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