Cited by 755Receptor Mechanisms and SignalingComputational Drug Discovery MethodsNeuroscience and Neuropharmacology Research

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

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Kroeze, Wesley K, Sassano, Maria F, Huang, Xi-Ping, Lansu, Katherine, McCorvy, John D, Giguère, Patrick M, Sciaky, Noah, Roth, Bryan L·2015·Nature Structural & Molecular Biology

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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  • 52 non-olfactory GPCRs are categorized as Tdark, and new screening platforms have begun the process of illuminating them.

    “Although 52 non-olfactory GPCRs are categorized as Tdark, the availability of new screening platforms to discover chemical matter for these GPCRs has begun the process of illumination64,67,68.”

    From Unexplored therapeutic opportunities in the human genome (2018) · cites this paper as [67]

    The Results and Discussion describe PRESTO-TANGO screening of poorly annotated and orphan GPCRs and the discovery of new ligand–receptor interactions, supporting the claim that a screening platform has begun to illuminate understudied receptors. The paper does not give a count of 52 non-olfactory GPCRs or classify them as Tdark; its Abstract instead discusses more than 100 orphan GPCRs. (LLM, conf=0.86)

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Authors
Kroeze, W. K., Sassano, M. F., Huang, X.-P., Lansu, K., McCorvy, J. D., Giguère, P. M., Sciaky, N., & Roth, B. L.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Roth, Bryan L
Venue
Nature Structural & Molecular Biology
Published
2015-04-20
Volume
22
Issue
5
Pages
362-369
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2036251618
Cited by
755
References
53
Citations by year
2026: 77 · 2025: 99 · 2024: 92 · 2023: 95 · 2022: 78 · 2021: 77 · 2020: 58 · 2019: 60 · 2018: 51 · 2017: 44 · 2016: 20 · 2015: 3
FWCI
17.21
Type
journal article
Language
en
Open access
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health (NIH T32)
  • National Institute of Mental Health (U19MH082441, U01MH104974, UO1MH104974)
  • National Institute on Drug Abuse (R01DA027170, R01DA27170)
  • National Institute of General Medical Sciences (NIH 5-T32-GM007040, T32GM007040)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
G protein-coupled receptors, orphan G protein-coupled receptor, high-throughput screening, β-arrestin recruitment, G protein-independent signaling, ligand discovery, transcriptional activation
MeSH terms
beta-Arrestins, Amino Acid Sequence, Biological Assay, Humans, Ligands, Transcription, Genetic, Transcriptional Activation, Arrestins, RNA Interference, RNA, Small Interfering, Receptors, G-Protein-Coupled

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