ArticlePloS one2021
Constitutive G protein coupling profiles of understudied orphan GPCRs.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Cryo-EM structures of GPR75 reveal an occluded orthosteric pocket challenging conventional drug discovery paradigms for an anti-obesity target.Acta pharmacologica Sinica · 2026Article
- GPR75 in glutamatergic neurons regulates body weight.Cell reports · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Orphan receptor GPR153 facilitates vascular damage responses by modulating cAMP levels, YAP/TAZ signaling, and NF-κB activation.Nature communications · 2025Article
- GNature communications · 2025Article
- Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways.Nature communications · 2025Article
- Exploring the constitutive activation mechanism of the class A orphan GPR20.Acta pharmacologica Sinica · 2025Article
- Adopting GPR75 in treating obesity: unraveling the knowns and unknowns of this orphan GPCR.Trends in cell biology · 2025Review
- Gz Enhanced Signal Transduction assaY (GbioRxiv : the preprint server for biology · 2024Article
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
- Lipid-Dependent Activation of the Orphan G Protein-Coupled Receptor, GPR3.Biochemistry · 2024Article
- GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions.Nucleic acids research · 2024Article
- Orphan G protein-coupled receptors: the ongoing search for a home.Frontiers in pharmacology · 2024Review
- Structural basis for ligand recognition and signaling of the lysophosphatidylserine receptors GPR34 and GPR174.PLoS biology · 2023Article
- Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive GNature communications · 2023Article
- Profiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform.Nature communications · 2023Article
- The role of G protein conformation in receptor-G protein selectivity.Nature chemical biology · 2023Article
- Article
- A peroxidase-derived ligand that inducesFrontiers in cellular and infection microbiology · 2023Article
- Atypical chemokine receptors: emerging therapeutic targets in cancer.Trends in pharmacological sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
A large number of GPCRs are potentially valuable drug targets but remain understudied. Many of these lack well-validated activating ligands and are considered "orphan" receptors, and G protein coupling profiles have not been defined for many orphan GPCRs. Here we asked if constitutive receptor activity can be used to determine G protein coupling profiles of orphan GPCRs. We monitored nucleotide-sensitive interactions between 48 understudied orphan GPCRs and five G proteins (240 combinations) using bioluminescence resonance energy transfer (BRET). No receptor ligands were used, but GDP was used as a common G protein ligand to disrupt receptor-G protein complexes. Constitutive BRET between the same receptors and β-arrestins was also measured. We found sufficient GDP-sensitive BRET to generate G protein coupling profiles for 22 of the 48 receptors we studied. Altogether we identified 48 coupled receptor-G protein pairs, many of which have not been described previously. We conclude that receptor-G protein complexes that form spontaneously in the absence of guanine nucleotides can be used to profile G protein coupling of constitutively-active GPCRs. This approach may prove useful for studying G protein coupling of other GPCRs for which activating ligands are not available.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.