ArticleNature chemical biology2021
Conformational rearrangement during activation of a metabotropic glutamate receptor.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 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
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- Domain coupling in activation of a family C GPCR.Nature chemical biology · 2025Article
- Direct effect of membrane environment on the activation of mGluR2 revealed by single-molecule FRET.Structure (London, England : 1993) · 2025Article
- Single-Molecule Insights into GPCR Conformational Landscapes.The Journal of membrane biology · 2025Review
- Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.Nature communications · 2024Article
- mGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.Pharmacological reports : PR · 2024Review
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.Nature communications · 2024Article
- Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization.Nature communications · 2024Article
- Article
- Exploring GPCR conformational dynamics using single-molecule fluorescence.Methods (San Diego, Calif.) · 2024Review
- Exploring the activation mechanism of metabotropic glutamate receptor 2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Homo- and hetero-dimeric subunit interactions set affinity and efficacy in metabotropic glutamate receptors.Nature communications · 2023Article
- Single-molecule visualization of human ACommunications biology · 2023Article
- Trends in Single-Molecule Total Internal Reflection Fluorescence Imaging and Their Biological Applications with Lab-on-a-Chip Technology.Sensors (Basel, Switzerland) · 2023Review
- Modulation of a conformational ensemble by a small molecule that inhibits key protein-protein interactions involved in cell adhesion.Protein science : a publication of the Protein Society · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) relay information across cell membranes through conformational coupling between the ligand-binding domain and cytoplasmic signaling domain. In dimeric class C GPCRs, the mechanism of this process, which involves propagation of local ligand-induced conformational changes over 12 nm through three distinct structural domains, is unknown. Here, we used single-molecule FRET and live-cell imaging and found that metabotropic glutamate receptor 2 (mGluR2) interconverts between four conformational states, two of which were previously unknown, and activation proceeds through the conformational selection mechanism. Furthermore, the conformation of the ligand-binding domains and downstream domains are weakly coupled. We show that the intermediate states act as conformational checkpoints for activation and control allosteric modulation of signaling. Our results demonstrate a mechanism for activation of mGluRs where ligand binding controls the proximity of signaling domains, analogous to some receptor kinases. This design principle may be generalizable to other biological allosteric sensors.
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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.