ArticleeLife2022
Conformational fingerprinting of allosteric modulators in metabotropic glutamate receptor 2.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
- Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.Science advances · 2026Article
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- Subtype-dependent arrestin engagement of the metabotropic glutamate receptors.Nature communications · 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
- GPCR drug discovery: new agents, targets and indications.Nature reviews. Drug discovery · 2025Review
- Direct effect of membrane environment on the activation of mGluR2 revealed by single-molecule FRET.Structure (London, England : 1993) · 2025Article
- Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.Nature communications · 2024Article
- Positive allosteric modulation of a GPCR ternary complex.Science advances · 2024Article
- Exploring GPCR conformational dynamics using single-molecule fluorescence.Methods (San Diego, Calif.) · 2024Review
- Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Concerted conformational changes control metabotropic glutamate receptor activity.Science advances · 2023Article
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Allosteric modulation of G protein-coupled receptor signaling.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Activation of G protein-coupled receptors (GPCRs) is an allosteric process. It involves conformational coupling between the orthosteric ligand binding site and the G protein binding site. Factors that bind at non-cognate ligand binding sites to alter the allosteric activation process are classified as allosteric modulators and represent a promising class of therapeutics with distinct modes of binding and action. For many receptors, how modulation of signaling is represented at the structural level is unclear. Here, we developed fluorescence resonance energy transfer (FRET) sensors to quantify receptor modulation at each of the three structural domains of metabotropic glutamate receptor 2 (mGluR2). We identified the conformational fingerprint for several allosteric modulators in live cells. This approach enabled us to derive a receptor-centric representation of allosteric modulation and to correlate structural modulation to the standard signaling modulation metrics. Single-molecule FRET analysis revealed that a NAM (egative allosteric modulator) increases the occupancy of one of the intermediate states while a positive allosteric modulator increases the occupancy of the active state. Moreover, we found that the effect of allosteric modulators on the receptor dynamics is complex and depend on the orthosteric ligand. Collectively, our findings provide a structural mechanism of allosteric modulation in mGluR2 and suggest possible strategies for design of future modulators.
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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.