ArticleThe Journal of biological chemistry2009
Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacy.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Dynamics and Interplay of the Binding Pockets in the Glycine Receptor.Journal of chemical information and modeling · 2025Article
- Illumination of a progressive allosteric mechanism mediating the glycine receptor activation.Nature communications · 2023Article
- Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3.Sub-cellular biochemistry · 2021Review
- String method solution of the gating pathways for a pentameric ligand-gated ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization.Scientific reports · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity.British journal of pharmacology · 2015Article
- Glycine receptor mouse mutants: model systems for human hyperekplexia.British journal of pharmacology · 2013Review
- Regulation of the surface expression of α4β2δ GABAA receptors by high efficacy states.Brain research · 2012Article
- Distinct properties of glycine receptor β+/α- interface: unambiguously characterizing heteromeric interface reconstituted in homomeric protein.The Journal of biological chemistry · 2012Article
- Charge and geometry of residues in the loop 2 β hairpin differentially affect agonist and ethanol sensitivity in glycine receptors.The Journal of pharmacology and experimental therapeutics · 2012Article
- Predicting flexible loop regions that interact with ligands: the challenge of accurate scoring.Proteins · 2012Article
- Glycine receptor mutants of the mouse: what are possible routes of inhibitory compensation?Frontiers in molecular neuroscience · 2012Article
- Activation and desensitization induce distinct conformational changes at the extracellular-transmembrane domain interface of the glycine receptor.The Journal of biological chemistry · 2011Article
- Contributions of conserved residues at the gating interface of glycine receptors.The Journal of biological chemistry · 2011Article
- A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonists.Molecular pharmacology · 2011Article
- A structural and mutagenic blueprint for molecular recognition of strychnine and d-tubocurarine by different cys-loop receptors.PLoS biology · 2011Article
- Crystal structures of a cysteine-modified mutant in loop D of acetylcholine-binding protein.The Journal of biological chemistry · 2011Article
- Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids.PloS one · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of agonists at Cys-loop ion channel receptors is determined by the rate they isomerize receptors to a pre-open flip state. Once the flip state is reached, the shut-open reaction is similar for low and high efficacy agonists. The present study sought to identify a conformational change associated with the closed-flip transition in the alpha1-glycine receptor. We employed voltage-clamp fluorometry to compare ligand-binding domain conformational changes induced by the following agonists, listed from highest to lowest affinity and efficacy: glycine > beta-alanine > taurine. Voltage-clamp fluorometry involves labeling introduced cysteines with environmentally sensitive fluorophores and inferring structural rearrangements from ligand-induced fluorescence changes. Agonist affinity and efficacy correlated inversely with maximum fluorescence magnitudes at labeled residues in ligand-binding domain loops D and E, suggesting that large conformational changes in this region preclude efficacious gating. However, agonist affinity and efficacy correlated directly with maximum fluorescence magnitudes from a label attached to A52C in loop 2, near the transmembrane domain interface. Because glycine experiences the largest affinity increase between closed and flip states, we propose that the magnitude of this fluorescence signal is directly proportional to the agonist affinity increase. In contrast, labeled residues in loops C, F, and the pre-M1 domain yielded agonist-independent fluorescence responses. Our results support the conclusion that a closed-flip conformation change, with a magnitude proportional to the agonist affinity increase from closed to flip states, occurs in the microenvironment of Ala-52.
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