ArticleNature communications2022
Molecular mechanism of agonism and inverse agonism in ghrelin receptor.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2.Cell research · 2026Article
- The Orally Available Ghrelin Receptor-Agonist AC01 Improves Systolic Function in HFrEF Mice and Nonhuman Primates.JACC. Basic to translational science · 2026Article
- Docking of virtual libraries identifies small-molecule agonists of neurotensin receptors with analgesic activity.Nature communications · 2026Article
- Membrane cholesterol modulates engagement of β-arrestin with the ghrelin receptor.Communications biology · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Strategic advances for cryo-EM structural studies of small (<100 kDa) GPCRs.Communications biology · 2026Review
- Molecular recognition of two approved drugs Macimorelin and Anamorelin by the growth hormone secretagogue receptor.Acta pharmacologica Sinica · 2025Article
- State-Specific Peptide Design Targeting G Protein-Coupled Receptors.Journal of chemical information and modeling · 2025Article
- Missense Variants in Nutrition-Related Genes: A Computational Study.International journal of molecular sciences · 2025Article
- MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants.bioRxiv : the preprint server for biology · 2025Article
- Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress.International journal of molecular sciences · 2025Article
- Ghrelin-LEAP2 interactions along the stomach-liver axis.Endocrine journal · 2025Review
- The structure and function of the ghrelin receptor coding for drug actions.Nature structural & molecular biology · 2025Article
- Naringenin Decreases Retroperitoneal Adiposity and Improves Metabolic Parameters in a Rat Model of Western Diet-Induced Obesity.Metabolites · 2025Article
- How the ghrelin receptor recognizes the acyl-modified orexigenic hormone.Frontiers in molecular neuroscience · 2025Review
- An atomic look at the interface of GHSR and its partners.Computational and structural biotechnology journal · 2024Article
- Structural basis of tethered agonism and G protein coupling of protease-activated receptors.Cell research · 2024Article
- Backbone Modification Provides a Long-Acting Inverse Agonist of Pathogenic, Constitutively Active PTH1R Variants.Journal of the American Chemical Society · 2024Article
- A survey of stapling methods to increase affinity, activity, and stability of ghrelin analogues.RSC medicinal chemistry · 2024Article
- Enhancement of transcription efficiency by TAR-Tat system increases the functional expression of human olfactory receptors.PloS one · 2024Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors.
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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.