ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
An arginine involved in GABA binding and unbinding but not gating of the GABA(A) receptor.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Introducing a proline in the α1 M2-M3 linker relieves a molecular brake on channel activation in α1β2γ2 GABAA receptors.PloS one · 2026Article
- GABAFrontiers in cellular neuroscience · 2020Article
- Loop G in the GABAThe Journal of physiology · 2017Article
- A role for loop G in the β1 strand in GABAA receptor activation.The Journal of physiology · 2016Article
- An Electrostatic Funnel in the GABA-Binding Pathway.PLoS computational biology · 2016Article
- Role ofBiochemistry and biophysics reports · 2015Article
- A molecular characterization of the agonist binding site of a nematode cys-loop GABA receptor.British journal of pharmacology · 2015Article
- γ-aminobutyric acid type A α4, β2, and δ subunits assemble to produce more than one functionally distinct receptor type.Molecular pharmacology · 2014Article
- Crystal structure of a human GABAA receptor.Nature · 2014Article
- Photo-antagonism of the GABAA receptor.Nature communications · 2014Article
- A nonequilibrium binary elements-based kinetic model for benzodiazepine regulation of GABAA receptors.The Journal of general physiology · 2014Article
- α1F64 Residue at GABA(A) receptor binding site is involved in gating by influencing the receptor flipping transitions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Multiple tyrosine residues at the GABA binding pocket influence surface expression and mediate kinetics of the GABAA receptor.Journal of neurochemistry · 2013Article
- Partial agonism of taurine at gamma-containing native and recombinant GABAA receptors.PloS one · 2013Article
- A unified model of the GABA(A) receptor comprising agonist and benzodiazepine binding sites.PloS one · 2013Article
- GABA binding to an insect GABA receptor: a molecular dynamics and mutagenesis study.Biophysical journal · 2012Article
- Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- A tight coupling between β₂Y97 and β₂F200 of the GABA(A) receptor mediates GABA binding.Journal of neurochemistry · 2011Article
- Three arginines in the GABAA receptor binding pocket have distinct roles in the formation and stability of agonist- versus antagonist-bound complexes.Molecular pharmacology · 2011Article
- New insights into the GABA(A) receptor structure and orthosteric ligand binding: receptor modeling guided by experimental data.Proteins · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
GABA(A) receptor function can be conceptually divided into interactions between ligand and receptor (binding) and the opening and closing of the ligand-bound channel (gating). The relationship between binding, gating, and receptor structure remains unclear. Studies of mutations have identified many amino acid residues that contribute to the GABAbinding site. Most of these studies assayed changes in GABA dose-response curves, which are macroscopic measures that depend on the interplay of many processes and cannot resolve individual microscopic transitions. Understanding the microscopic basis of binding and gating is critical, because kinetic transition rates predict how receptors will behave at synapses. Furthermore, microscopic rates are directly related to the molecular interactions underlying receptor function. Here, we focused on a residue (beta2-R207) previously identified as lining the GABA-binding site that, when mutated to cysteine, greatly reduces apparent GABA affinity and was predicted to affect both binding and gating. To better understand the role of beta2-R207, we expressed alpha1beta2 and alpha1beta2-R207C receptors in human embryonic kidney 293 cells and studied receptor kinetics using fast solution applications. The mutation accelerated deactivation by 10-fold, without altering desensitization in the presence of saturating GABA. Maximum open probability and single-channel open times were also unaltered by the mutation, but the GABA-binding rate was reduced eightfold. Therefore, the effects of this mutation in a predicted binding site residue are solely attributable to changes in GABA-binding and unbinding kinetics, with no changes in channel gating. Because beta2-R207 stabilizes GABA in the binding pocket, it may directly contact the GABA molecule.
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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.