ArticleProceedings of the National Academy of Sciences of the United States of America2021
A nanobody activating metabotropic glutamate receptor 4 discriminates between homo- and heterodimers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Multivalent antibody-based conjugates as new tools for tailored modulation of G protein-coupled receptors.British journal of pharmacology · 2026Review
- 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
- Nanobodies unlock new mechanisms to target G protein-coupled receptors.Molecular pharmacology · 2026Review
- Targeting mGlyR with nanobodies for depression.Nature communications · 2026Article
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.Nature communications · 2025Article
- Development of an allosteric adhesion GPCR nanobody with therapeutic potential.Nature chemical biology · 2025Article
- Article
- Progress toward new function and design of extracellular G protein-coupled receptor nanobodies.Molecular pharmacology · 2025Review
- Epitope-directed selection of GPCR nanobody ligands with evolvable function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.bioRxiv : the preprint server for biology · 2024Article
- The process using a synthetic library that generates multiple diverse human single domain antibodies.Antibody therapeutics · 2024Article
- The Impact of Nanobodies on G Protein-Coupled Receptor Structural Biology and Their Potential as Therapeutic Agents.Molecular pharmacology · 2024Review
- Homo- and hetero-dimeric subunit interactions set affinity and efficacy in metabotropic glutamate receptors.Nature communications · 2023Article
- Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.Science advances · 2023Article
- Combined Multiplexed Phage Display, High-Throughput Sequencing, and Functional Assays as a Platform for Identifying Modulatory VHHs Targeting the FSHR.International journal of molecular sciences · 2023Article
- Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic.International journal of molecular sciences · 2023Review
- Concerted conformational changes control metabotropic glutamate receptor activity.Science advances · 2023Article
- Targeting the Brain with Single-Domain Antibodies: Greater Potential Than Stated So Far?International journal of molecular sciences · 2023Review
- Nanobody-based sensors reveal a high proportion of mGlu heterodimers in the brain.Nature chemical biology · 2022Article
- Accelerating GPCR Drug Discovery With Conformation-Stabilizing VHHs.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is growing interest in developing biologics due to their high target selectivity. The G protein-coupled homo- and heterodimeric metabotropic glutamate (mGlu) receptors regulate many synapses and are promising targets for the treatment of numerous brain diseases. Although subtype-selective allosteric small molecules have been reported, their effects on the recently discovered heterodimeric receptors are often not known. Here, we describe a nanobody that specifically and fully activates homodimeric human mGlu4 receptors. Molecular modeling and mutagenesis studies revealed that the nanobody acts by stabilizing the closed active state of the glutamate binding domain by interacting with both lobes. In contrast, this nanobody does not activate the heterodimeric mGlu2-4 but acts as a pure positive allosteric modulator. These data further reveal how an antibody can fully activate a class C receptor and bring further evidence that nanobodies represent an alternative way to specifically control mGlu receptor subtypes.
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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.