ArticleNature chemical biology2025
Development of an allosteric adhesion GPCR nanobody with therapeutic potential.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed.
- Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 2026Review
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- GPCRs in CAR-T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Dehydroepiandrosterone activates ADGRG2 to regulate chloride homeostasis and sperm motility via Gs-cAMP pathways.Science China. Life sciences · 2026Article
- Nanobodies unlock new mechanisms to target G protein-coupled receptors.Molecular pharmacology · 2026Review
- Nanobodies targeting the Epstein-Barr virus EBNA1 DNA binding domain inhibit tumor growth.Journal of nanobiotechnology · 2026Article
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury.Bone research · 2026Review
- Molecular insights into ligand recognition and signaling of OXGR1.Nature communications · 2025Article
- Engineering antibody-drug conjugates targeting an adhesion GPCR, CD97.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors.
Funding
Abstract
Allosteric modulation of receptor responses to endogenous agonists has therapeutic value, maintaining ligand profiles, reducing side effects and restoring mutant responses. Adhesion G-protein-coupled receptors (aGPCRs), with large N termini, are ideal for allosteric modulator development. We designed a nanobody strategy targeting ADGRG2 N-terminal fragments and got a specific nanobody Nb23-bi, which promoted dehydroepiandrosterone (DHEA)-induced ADGRG2 activation and reversed mutant-induced dysfunctions. By combining structural characterization, crosslinking mass spectrometry, mutational analysis and molecular dynamics simulations, we clarified the allosteric mechanism of how the Nb23-bi modulates conformational changes in the DHEA-binding pocket. Animal studies showed that Nb23-bi promoted the response of DHEA in alleviating testicular inflammation and reversing mutant defects. In summary, we developed an allosteric nanobody of ADGRG2 and gained insights into its functions in reversing disease-associated dysfunctions. Our study may serve as a template for developing allosteric modulators of other aGPCRs for biological and therapeutic purposes.
Indexed as
Identifiers
40374856What OpenQuestion holds
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.