ArticleNature communications2023
Cryo-EM structures of orphan GPR21 signaling complexes.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- CVN-424: An Advanced GPR6 Inverse Agonist in Phase III Clinical Trials for Parkinson's Disease.Journal of medicinal chemistry · 2026Article
- Structure of the melatonin-related orphan receptor, GPR50.Molecules and cells · 2026Article
- Ligand binding modes of the bitter taste receptor T2R14 and T2R46.Nature structural & molecular biology · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Structural analysis reveals that water molecules mediate self-activation of GPR99.Communications biology · 2026Article
- Orphan GPCRs in diabetes mellitus: metabolic control, inflammation, and drug development.Frontiers in endocrinology · 2026Review
- Constitutive arrestin recruitment by orphan GPR52 via an atypical binding mode.Cell research · 2025Article
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- Monoclonal Antibody 5F1 Modulates Formyl Peptide Receptor 1 Conformation for Transmembrane Signaling.FASEB bioAdvances · 2025Article
- Structural insight into the self-activation and G-protein coupling of P2Y2 receptor.Cell discovery · 2025Article
- The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer.Nature communications · 2024Article
- Review
- Constitutive activation mechanism of a class C GPCR.Nature structural & molecular biology · 2024Article
- Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8.Science advances · 2024Article
- A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways.Cell discovery · 2024Article
- Structure, function and drug discovery of GPCR signaling.Molecular biomedicine · 2023Review
- An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism.Nature communications · 2023Article
- Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive GNature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling to multiple G proteins in the absence of any known endogenous agonist or synthetic ligand. Here, we present the structures of ligand-free human GPR21 bound to heterotrimeric miniGs and miniG15 proteins, respectively. We identified an agonist-like motif in extracellular loop 2 (ECL2) that occupies the orthosteric pocket and promotes receptor activation. A side pocket that may be employed as a new ligand binding site was also uncovered. Remarkably, G protein binding is accommodated by a flexible cytoplasmic portion of transmembrane helix 6 (TM6) which adopts little or undetectable outward movement. These findings will enable the design of modulators for GPR21 for understanding its signal transduction and exploring opportunity for deorphanization.
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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 Socratic graph.