ArticleNature chemical biology2024
Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Decreased cerebrospinal fluid TNFRSF8 (sCD30) confirmed as a biomarker of Huntington's disease progression.Journal of neurology · 2026Article
- Molecular Dynamics and Free Energy Calculations Predict Binding Mode and Affinity Determinants of Specialized Pro-Resolving Mediators at GPR101.ACS omega · 2026Article
- 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
- Structure-based screening and a conformational biosensor identify a GPR183 inverse agonist and an activation switch.Nature communications · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Comparing models and experimental structures of the GPR101 receptor: Artificial intelligence yields highly accurate models.Journal of molecular graphics & modelling · 2025Article
- Cellular senescence in kidney diseases.Chinese medical journal · 2025Review
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- A force-sensitive adhesion GPCR is required for equilibrioception.Cell research · 2025Article
- Chromatin conformation capture in the clinic: 4C-seq/HiC distinguishes pathogenic from neutral duplications at the GPR101 locus.Genome medicine · 2024Article
- The sphingosine-1-phosphate receptor 1 mediates the atheroprotective effect of eicosapentaenoic acid.Nature metabolism · 2024Article
- Computational Methods for the Discovery and Optimization of TAAR1 and TAAR5 Ligands.International journal of molecular sciences · 2024Review
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- GPR101: Modeling a constitutively active receptor linked to X-linked acrogigantism.Journal of molecular graphics & modelling · 2024Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
Abstract
GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.
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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.