PRESTO-TANGO: an open-source resource for interrogation of the druggable human GPCR-ome

By W. Kroeze, M. F. Sassano, Xi-Ping Huang, K. Lansu, J. McCorvy, P. Giguère, N. Sciaky, Bryan L. Roth. Nature Structural &Molecular Biology, 2015

610 citations recorded by the source corpus.

G protein–coupled receptors (GPCRs) are essential mediators of cellular signaling and are important targets of drug action. Of the approximately 350 nonolfactory human GPCRs, more than 100 are still considered to be 'orphans' because their endogenous ligands remain unknown. Here, we describe a unique open-source resource that allows interrogation of the druggable human GPCRome via a G protein–independent β-arrestin–recruitment assay. We validate this unique platform at more than 120 nonorphan human GPCR targets, demonstrate its utility for discovering new ligands for orphan human GPCRs and describe a method (parallel receptorome expression and screening via transcriptional output, with transcriptional activation following arrestin translocation (PRESTO-Tango)) for the simultaneous and parallel interrogation of the entire human nonolfactory GPCRome.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/97402c7e843b88236c609e68d2860537d7326a56

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Citations in the corpus

Diverse Functional Autoantibodies in Patients with COVID-19 (2020, positive): “Similarly, we assayed chemokine receptor activity using the PRESTO-Tango system 20 and found that serum-purified IgG from a patient with anti-CXCL7 autoantibodies and a patient with anti-CXCL1 autoantibodies neutralized CXCL7 and CXCL1 signaling on their shared receptor CXCR2, whereas…”
Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors (2019, methodology): “The third, the b-arrestin recruitment assay, is a highly amplified reporter gene-based readout of GPCR signaling (Kroeze et al., 2015) that increases the sensitivity of detecting positive pairings and allowed us to rapidly screen an additional 46 orphan/understudied and 27 known peptide-activated cl”
Synthon-based ligand discovery in virtual libraries of over 11 billion compounds (2021, methodology): “The Tango arrestin recruitment assays were performed as previously described 23 .”
A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice (2018, methodology): “Luciferase reporter cell line for tango assay (Kroeze et al., 2015) Gift from Bryan L Roth N/A”
DREADDs for Neuroscientists (2016, background): “Additionally, new chemical biology platforms that allow for the unbiased assessment of on- and off-target pharmacologies of chemical actuators across the GPCR-ome (Kroeze et al., 2015), kinome (Elkins et al., 2015), and other targets (Arrowsmith et al., 2015) are key to validating the specificity of”