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PMID: 25895059 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

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

Nature structural & molecular biology ·Vol. 22 ·No. 5 ·2015-05-00 ·Pages 362-9

Kroeze WK, Sassano MF, Huang XP, Lansu K, McCorvy JD, Giguère PM, Sciaky N, Roth BL

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.

MeSH Terms
Amino Acid Sequence Arrestins/metabolism Biological Assay/methods Humans Ligands RNA Interference RNA, Small Interfering Receptors, G-Protein-Coupled/agonists,antagonists & inhibitors,metabolism Transcription, Genetic Transcriptional Activation beta-Arrestins
Chemicals
Arrestins Ligands RNA, Small Interfering Receptors, G-Protein-Coupled beta-Arrestins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kroeze Wesley K
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.
Sassano Maria F
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.
Huang Xi-Ping
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.
Lansu Katherine
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
McCorvy John D
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
Giguère Patrick M
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
Sciaky Noah
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
Roth Bryan L
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.
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.3014
Published
2015-05-00
Epub
2015-00-20
Pages
362-9
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC4424118
Subset
IM
Grants
NIDA NIH HHS · R01 DA027170 · United States
NIMH NIH HHS · U19 MH082441 · United States
NIGMS NIH HHS · T32 GM007040 · United States
NIDA NIH HHS · R01DA27170 · United States
Intramural NIH HHS · United States
NIMH NIH HHS · UO1MH104974 · United States
NIGMS NIH HHS · NIH 5-T32-GM007040 · United States
NIMH NIH HHS · U01 MH104974 · United States
External Links
PubMed source DOI: 10.1038/nsmb.3014 PMC Full Text View journal details
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