ArticleeLife2021
Differences in interactions between transmembrane domains tune the activation of metabotropic glutamate receptors.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
- Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins.Nature communications · 2026Article
- GPCR Sense Communication Among Interaction Nematodes with Other Organisms.International journal of molecular sciences · 2025Review
- 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
- Therapeutic Potential for Metabotropic Glutamate Receptor 7 Modulators in Cognitive Disorders.Molecular pharmacology · 2024Review
- Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.Cell reports · 2024Article
- Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.Science advances · 2023Article
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Physiology, Pharmacology, and Genetics.Molecules (Basel, Switzerland) · 2023Review
- The crosstalk between 5-HTNeuropharmacology · 2023Review
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Kinetic fingerprinting of metabotropic glutamate receptors.Communications biology · 2023Article
- Sulfonated red and far-red rhodamines to visualize SNAP- and Halo-tagged cell surface proteins.Organic & biomolecular chemistry · 2022Article
- Conformational fingerprinting of allosteric modulators in metabotropic glutamate receptor 2.eLife · 2022Article
- Structural and compositional diversity in the kainate receptor family.Cell reports · 2021Article
- Asymmetry is central to excitatory glutamate receptor activation.Nature structural & molecular biology · 2021Article
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Authors and funding
12 authors.
Funding
Abstract
The metabotropic glutamate receptors (mGluRs) form a family of neuromodulatory G-protein-coupled receptors that contain both a seven-helix transmembrane domain (TMD) and a large extracellular ligand-binding domain (LBD) which enables stable dimerization. Although numerous studies have revealed variability across subtypes in the initial activation steps at the level of LBD dimers, an understanding of inter-TMD interaction and rearrangement remains limited. Here, we use a combination of single molecule fluorescence, molecular dynamics, functional assays, and conformational sensors to reveal that distinct TMD assembly properties drive differences between mGluR subtypes. We uncover a variable region within transmembrane helix 4 (TM4) that contributes to homo- and heterodimerization in a subtype-specific manner and tunes orthosteric, allosteric, and basal activation. We also confirm a critical role for a conserved inter-TM6 interface in stabilizing the active state during orthosteric or allosteric activation. Together this study shows that inter-TMD assembly and dynamic rearrangement drive mGluR function with distinct properties between subtypes.
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