ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
No ligand binding in the GB2 subunit of the GABA(B) receptor is required for activation and allosteric interaction between the subunits.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 151 citations in OpenAlex.
- GABA-independent activation of GABANature communications · 2025Article
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- Orphan G protein-coupled receptors: the ongoing search for a home.Frontiers in pharmacology · 2024Review
- GABACurrent topics in behavioral neurosciences · 2022Article
- GABACurrent topics in behavioral neurosciences · 2022Review
- Structural Characterization of Receptor-Receptor Interactions in the Allosteric Modulation of G Protein-Coupled Receptor (GPCR) Dimers.International journal of molecular sciences · 2021Review
- Rational approaches for the design of various GABA modulators and their clinical progression.Molecular diversity · 2021Review
- Ectopic activation of GABANature ecology & evolution · 2021Article
- The GABAMolecules (Basel, Switzerland) · 2020Review
- Exploring Conformational Dynamics of the ExtracellularJournal of chemical information and modeling · 2020Article
- In Silico Methods for the Discovery of Orthosteric GABAMolecules (Basel, Switzerland) · 2019Article
- Structural biology of GABANeuropharmacology · 2018Review
- Review
- Towards a Better Understanding of GABAergic Remodeling in Alzheimer's Disease.International journal of molecular sciences · 2017Review
- Class C G protein-coupled receptors: reviving old couples with new partners.Biophysics reports · 2017Article
- GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper.Molecular psychiatry · 2016Article
- Activation of the γ-Aminobutyric Acid Type B (GABA(B)) Receptor by Agonists and Positive Allosteric Modulators.Journal of medicinal chemistry · 2015Review
- Hunting for the function of orphan GPCRs - beyond the search for the endogenous ligand.British journal of pharmacology · 2015Review
- GABA Receptors Genes Polymorphisms and Alcohol Dependence: No Evidence of an Association in an Italian Male Population.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2014Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The GABA(B) receptor plays important roles in the tuning of many synapses. Although pharmacological differences have been observed between various GABA(B)-mediated effects, a single GABA(B) receptor composed of two subunits (GB1 and GB2) has been identified. Although GB1 binds GABA, GB2 plays a critical role in G-protein activation. Moreover, GB2 is required for the high agonist affinity of GB1. Like any other family 3 G-protein-coupled receptors, GB1 and GB2 are composed of a Venus Flytrap module (VFTM) that usually contains the agonist-binding site and a heptahelical domain. So far, there has been no direct demonstration that GB2 binds GABA or another endogenous ligand. Here, we have further refined the GABA-binding site of GB1 and characterized the putative-binding site in the VFTM of GB2. None of the residues important for GABA binding in GB1 appeared to be conserved in GB2. Moreover, mutation of 10 different residues, alone or in combination, within the possible binding pocket of GB2 affects neither GABA activation of the receptor nor the ability of GB2 to increase agonist affinity on GB1. These data indicate that ligand binding in the GB2 VFTM is not required for activation. Finally, although in either GB1 or the related metabotropic glutamate receptors most residues of the binding pocket are conserved from Caenorhabditis elegans to human, no such conservation is observed in GB2. This suggests that the GB2 VFTM does not constitute a binding site for a natural ligand.
Indexed as
Identifiers
12196556PMC6757956W2128780400What 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.