ArticleProceedings of the National Academy of Sciences of the United States of America2022
Structural insights into galanin receptor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Review
- Galanin Receptors in the Central Nervous System: Exploring Ligand Interactions, Signal Transduction, and Potential Clinical Implications.Molecules (Basel, Switzerland) · 2026Review
- Structural and dynamic insights into agonist recognition and function of the thromboxane ANature communications · 2026Article
- Galanin Receptors: G Protein-Dependent Signaling and Beyond.Biomolecules · 2026Review
- Biochemical and Physiological Effects of Galanin in Health and Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Emerging roles of spexin in cardiovascular homeostasis.Frontiers in cardiovascular medicine · 2026Review
- The Allosteric Mechanism of G-Protein-Coupled Receptors is Induced Fit, Not Conformational Selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- FDA Drug Repurposing Uncovers Modulators of Dopamine DJournal of medicinal chemistry · 2025Article
- Structural insights into the G-protein subtype selectivity revealed by human sphingosine-1-phosphate receptor 3-GProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The polypharmacology of psychedelics reveals multiple targets for potential therapeutics.Neuron · 2025Article
- Development of a HiBiT Peptide-Based NanoBRET Ligand Binding Assay for Galanin Receptor 1 in Live Cells.ACS chemical biology · 2025Article
- Structural insight into the self-activation and G-protein coupling of P2Y2 receptor.Cell discovery · 2025Article
- Structural visualization of small molecule recognition by CXCR3 uncovers dual-agonism in the CXCR3-CXCR7 system.Nature communications · 2025Article
- Neuropeptides: The Evergreen Jack-of-All-Trades in Neuronal Circuit Development and Regulation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Effects of celastrol on the heart and liver galaninergic system expression in a mouse model of Western-type diet-induced obesity and metabolic dysfunction-associated steatotic liver disease and steatohepatitis.Frontiers in pharmacology · 2025Article
- Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive GNature communications · 2023Article
- Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4).Nature communications · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Galanin is a biologically active neuropeptide, and functions through three distinct G protein–coupled receptors (GPCRs), namely GALR1, GALR2, and GALR3. GALR signaling plays important roles in regulating various physiological processes such as energy metabolism, neuropathic pain, epileptic activity, and sleep homeostasis. GALR1 and GALR3 signal through the Gi/o pathway, whereas GALR2 signals mainly through the Gq/11 pathway. However, the molecular basis for galanin recognition and G protein selectivity of GALRs remains poorly understood. Here, we report the cryoelectron microscopy structures of the GALR1-Go and the GALR2-Gq complexes bound to the endogenous ligand galanin or spexin. The galanin peptide mainly adopts an alpha helical structure, which binds at the extracellular vestibule of the receptors, nearly parallel to the membrane plane without penetrating deeply into the receptor core. Structural analysis combined with functional studies reveals important structural determinants for the G protein selectivity of GALRs as well as other class A GPCRs. In addition, we show that the zinc ion is a negative allosteric regulator of GALR1 but not GALR2. Our studies provide insight into the mechanisms of G protein selectivity of GPCRs and highlight a potential function of the neuromodulator zinc ion as a modulator of GPCR signaling in the central nervous system.
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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.