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Nat Struct Mol Biol. 2015 May;22(5):362-9. doi: 10.1038/nsmb.3014. Epub 2015 Apr 20.

PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome.

Author information

1
1] 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.
2
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
3
1] 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. [3] Program in Neuroscience, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [4] Division of Chemical Biology and Medicinal Chemistry, 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.

PMID:
25895059
PMCID:
PMC4424118
DOI:
10.1038/nsmb.3014
[Indexed for MEDLINE]
Free PMC Article

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