ArticleScience advances2023
Concerted conformational changes control metabotropic glutamate receptor activity.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- Allosteric activation of the glutamate receptor mGlu2 by the serotonin receptor 5-HTNature communications · 2026Article
- Advancing Single-Molecule Biophysics: Next-Generation Organic Fluorophores with Tailored Labeling Strategies.Chemical & biomedical imaging · 2025Review
- Domain coupling in activation of a family C GPCR.Nature chemical biology · 2025Article
- Resolving the conformational ensemble of a membrane protein by integrating small-angle scattering with AlphaFold.PLoS computational biology · 2025Article
- Triple Labeling Resolves a GPCR Intermediate State by Using Three-Color Single Molecule FRET.Journal of the American Chemical Society · 2025Article
- Conformational diversity in class C GPCR positive allosteric modulation.Nature communications · 2025Article
- mGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.Pharmacological reports : PR · 2024Review
- Structural basis of orientated asymmetry in a mGlu heterodimer.Nature communications · 2024Article
- Positive allosteric modulation of a GPCR ternary complex.Science advances · 2024Article
- 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
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allosteric modulators bear great potential to fine-tune neurotransmitter action. Promising targets are metabotropic glutamate (mGlu) receptors, which are associated with numerous brain diseases. Orthosteric and allosteric ligands act in synergy to control the activity of these multidomain dimeric GPCRs. Here, we analyzed the effect of such molecules on the concerted conformational changes of full-length mGlu2 at the single-molecule level. We first established FRET sensors through genetic code expansion combined with click chemistry to monitor conformational changes on live cells. We then used single-molecule FRET and show that orthosteric agonist binding leads to the stabilization of most of the glutamate binding domains in their closed state, while the reorientation of the dimer into the active state remains partial. Allosteric modulators, interacting with the transmembrane domain, are required to stabilize the fully reoriented active dimer. These results illustrate how concerted conformational changes within multidomain proteins control their activity, and how these are modulated by allosteric ligands.
Indexed as
Identifiers
What 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.