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Updated: Apr 14, 2026

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
Published on: March 10, 2020
PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome
Wesley K Kroeze1, Maria F Sassano1, Xi-Ping Huang1
11] Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [2] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract:
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.
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