ArticleNature communications2024
Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization.
Article in Nature communications, 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed.
- Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins.Nature communications · 2026Article
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
- Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid-β Production and Cognitive Dysfunctions in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synthesis of Novel Acetylene-Containing Phosphonates, Their Antiviral Activity, and Their Cytotoxicity to Different Cancer Cell Lines.Molecules (Basel, Switzerland) · 2026Article
- Transmembrane Domain Dominance Drives Emergent Signaling and Allosteric Inversion in mGlubioRxiv : the preprint server for biology · 2026Article
- Metabotropic Glutamate Receptor 3 Expression During Liver Disease Progression: Association with Inflammation and Cell Viability in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Cryo-EM Structures of Brain-Derived G Protein-Coupled Receptors: The First Direct Visualization from Mammalian Brain Tissue.bioRxiv : the preprint server for biology · 2026Article
- CryoEM structure of mGlu6 captures receptor activation prior to G protein coupling.Nature communications · 2026Article
- Microplastics and Nanoplastics Cause Thyroid Dysfunction in Adolescent Mice through the Intestinal Microbiota-Mediated Hypothalamus-Pituitary-Thyroid Axis.Environment & health (Washington, D.C.) · 2026Article
- Modulating glutamate neurotransmission inFrontiers in immunology · 2026Review
- Upregulation of NR2A in Glutamatergic VTA Neurons Contributes to Chronic Visceral Pain in Male Mice.Neuroscience bulletin · 2025Article
- Domain coupling in activation of a family C GPCR.Nature chemical biology · 2025Article
- Molecular Glues: A New Approach to Modulating GPCR Signaling Bias.Biochemistry · 2025Review
- Group III metabotropic glutamate receptors: guardians against excitotoxicity in ischemic brain injury, with implications for neonatal contexts.Pharmacological reports : PR · 2024Review
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15 authors.
Funding
Abstract
The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled receptors which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane domains (TMDs) to drive intracellular signaling. Pharmacologically, mGluRs can be targeted at the LBDs by glutamate and synthetic orthosteric compounds or at the TMDs by allosteric modulators. Despite the potential of allosteric compounds as therapeutics, an understanding of the functional and structural basis of their effects is limited. Here we use multiple approaches to dissect the functional and structural effects of orthosteric versus allosteric ligands. We find, using electrophysiological and live cell imaging assays, that both agonists and positive allosteric modulators (PAMs) can drive activation and internalization of group II and III mGluRs. The effects of PAMs are pleiotropic, boosting the maximal response to orthosteric agonists and serving independently as internalization-biased agonists across mGluR subtypes. Motivated by this and intersubunit FRET analyses, we determine cryo-electron microscopy structures of mGluR3 in the presence of either an agonist or antagonist alone or in combination with a PAM. These structures reveal PAM-driven re-shaping of intra- and inter-subunit conformations and provide evidence for a rolling TMD dimer interface activation pathway that controls G protein and beta-arrestin coupling.
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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.