ArticleThe Journal of biological chemistry
Optimization of a peptide ligand for the adhesion GPCR ADGRG2 provides a potent tool to explore receptor biology.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Dehydroepiandrosterone activates ADGRG2 to regulate chloride homeostasis and sperm motility via Gs-cAMP pathways.Science China. Life sciences · 2026Article
- Cytoplasmic tail diversity determines the effector bias of the adhesion GPCR ADGRL2.Cell chemical biology · 2026Article
- Development of an allosteric adhesion GPCR nanobody with therapeutic potential.Nature chemical biology · 2025Article
- Cytoplasmic tail composition modulates the G protein and arrestin-3 signaling bias of the adhesion GPCR LPHN2.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of Peptide Agonist Dissociation and Deactivation of Adhesion G-Protein-Coupled Receptors.Biochemistry · 2025Article
- Generic residue numbering of the GAIN domain of adhesion GPCRs.Nature communications · 2025Article
- Exploring the Binding Mechanism of ADGRG2 Through Metadynamics and Biochemical Analysis.International journal of molecular sciences · 2024Article
- Mechanisms of peptide agonist dissociation and deactivation of adhesion G-protein-coupled receptors.bioRxiv : the preprint server for biology · 2024Article
- Deciphering the role of glycosaminoglycans in GPCR signaling.Cellular signalling · 2024Review
- Mechanistic Insights into Peptide Binding and Deactivation of an Adhesion G Protein-Coupled Receptor.Molecules (Basel, Switzerland) · 2023Article
- Structures of the ADGRG2-GNature chemical biology · 2022Article
- Adhesion G protein-coupled receptor gluing action guides tissue development and disease.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.Physiological reviews · 2022Review
- Article
- Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia.Genes & genomics · 2022Article
- Mechanism of tethered agonist-mediated signaling by polycystin-1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Chemo- and mechanosensing by dendritic cells facilitate antigen surveillance in the spleen.Immunological reviews · 2022Review
- Conserved residues in the extracellular loop 2 regulate Stachel-mediated activation of ADGRG2.Scientific reports · 2021Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adhesion GPCR ADGRG2, also known as GPR64, is a critical regulator of male fertility that maintains ion/pH homeostasis and CFTR coupling. The molecular basis of ADGRG2 function is poorly understood, in part because no endogenous ligands for ADGRG2 have been reported, thus limiting the tools available to interrogate ADGRG2 activity. It has been shown that ADGRG2 can be activated by a peptide, termed p15, derived from its own N-terminal region known as the Stachel sequence. However, the low affinity of p15 limits its utility for ADGRG2 characterization. In the current study, we used alanine scanning mutagenesis to examine the critical residues responsible for p15-induced ADGRG2 activity. We next designed systematic strategies to optimize the peptide agonist of ADGRG2, using natural and unnatural amino acid substitutions. We obtained an optimized ADGRG2 Stachel peptide T1V/F3Phe(4-Me) (VPM-p15) that activated ADGRG2 with significantly improved (>2 orders of magnitude) affinity. We then characterized the residues in ADGRG2 that were important for ADGRG2 activation in response to VPM-p15 engagement, finding that the toggle switch W
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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.