ArticleMolecular pharmacology2011
A state-dependent salt-bridge interaction exists across the β/α intersubunit interface of the GABAA receptor.
Article in Molecular pharmacology, 2011. 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, 20 citations in OpenAlex.
- Physical and functional interaction sites in cytoplasmic domains of KCNQ1 and KCNE1 channel subunits.American journal of physiology. Heart and circulatory physiology · 2020Article
- GABAFrontiers in cellular neuroscience · 2020Article
- The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening.The Journal of general physiology · 2019Article
- Intersubunit interactions at putative sites of ethanol action in the M3 and M4 domains of the NMDA receptor GluN1 and GluN2B subunits.British journal of pharmacology · 2016Article
- A Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors.The Journal of biological chemistry · 2016Article
- Identification of critical functional determinants of kainate receptor modulation by auxiliary protein Neto2.The Journal of physiology · 2015Article
- Identification of amino acids involved in histamine potentiation of GABA A receptors.Frontiers in pharmacology · 2015Article
- 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
- SB-205384 is a positive allosteric modulator of recombinant GABAA receptors containing rat α3, α5, or α6 subunit subtypes coexpressed with β3 and γ2 subunits.The Journal of pharmacology and experimental therapeutics · 2013Article
- Insights on the mechanisms of Ca(2+) regulation of connexin26 hemichannels revealed by human pathogenic mutations (D50N/Y).The Journal of general physiology · 2013Article
- Interactions among positions in the third and fourth membrane-associated domains at the intersubunit interface of the N-methyl-D-aspartate receptor forming sites of alcohol action.The Journal of biological chemistry · 2012Article
- Highly conserved salt bridge stabilizes rigid signal patch at extracellular loop critical for surface expression of acid-sensing ion channels.The Journal of biological chemistry · 2012Article
- Sequences prior to conserved catalytic motifs of polysialyltransferase ST8Sia IV are required for substrate recognition.The Journal of biological chemistry · 2012Article
- A tight coupling between β₂Y97 and β₂F200 of the GABA(A) receptor mediates GABA binding.Journal of neurochemistry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The GABA(A) receptor is a multisubunit protein that transduces the binding of a neurotransmitter at an intersubunit interface into the opening of a central ion channel. The structural components that mediate the steps involved in this action are poorly defined. A large amount of work has focused on clarifying the specific functions and interactions of residues believed to surround the GABA binding pocket. Here, we explored two charged residues (β(2)Asp163 and α(1)Arg120), which have been suggested by homology models to participate in a salt-bridge interaction. When mutated to alanine, both single mutants, as well as the double mutant, increase EC(50-GABA), decrease the GABA binding rate, and accelerate deactivation and GABA unbinding rates. Double-mutant cycle analysis demonstrates that the effects of each alanine mutation on the GABA binding rate were additive and independent. In contrast, a significant coupling energy was found during an analysis of deactivation time constants. Using kinetic modeling, we further demonstrated that the GABA unbinding rates, in particular, are strongly coupled. These data suggest that β(2)Asp163 and α(1)Arg120 form a state-dependent salt bridge, interacting when GABA is bound to the receptor but not when the receptor is in the unbound state.
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.