ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms.The Journal of biological chemistry · 2013Trial
- Solvent-Isotope Effects in Biomolecular Phase Separation and Fibrillation of Disordered Proteins and Peptides.bioRxiv : the preprint server for biology · 2026Article
- Palladium-triggered bioorthogonal phenylalanine decaging.Nature chemistry · 2026Article
- Interplay of Noncovalent Interactions in Phase Separation Mediated by Tyrosine-Rich and Arginine-Rich Polypeptides.Journal of the American Chemical Society · 2026Article
- Chemical tuning reveals a cation-π gating bridge between the voltage-sensor and pore domains in the KProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Gating mechanism of the human α1β GlyR by glycine.Structure (London, England : 1993) · 2024Article
- Expression and purification of fluorinated proteins from mammalian suspension culture.Methods in enzymology · 2024Article
- Tinker, Tailor, Soldier, Spy: The Diverse Roles That Fluorine Can Play within Amino Acid Side Chains.Molecules (Basel, Switzerland) · 2023Review
- Article
- Cation-π Interactions and their Functional Roles in Membrane Proteins.Journal of molecular biology · 2021Review
- Thermophoretic analysis of ligand-specific conformational states of the inhibitory glycine receptor embedded in copolymer nanodiscs.Scientific reports · 2020Article
- A tale of ligands big and small: an update on how pentameric ligand-gated ion channels interact with agonists and proteins.Current opinion in physiology · 2019Article
- Multiple regions in the extracellular domain of the glycine receptor determine receptor activity.The Journal of biological chemistry · 2018Article
- The roles of aromatic residues in the glycine receptor transmembrane domain.BMC neuroscience · 2018Article
- The Startle Disease Mutation E103K Impairs Activation of Human Homomeric α1 Glycine Receptors by Disrupting an Intersubunit Salt Bridge across the Agonist Binding Site.The Journal of biological chemistry · 2017Article
- Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels.Scientific reports · 2015Article
- Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Incorporation of Non-Canonical Amino Acids.Advances in experimental medicine and biology · 2015Review
- Disturbances of Ligand Potency and Enhanced Degradation of the Human Glycine Receptor at Affected Positions G160 and T162 Originally Identified in Patients Suffering from Hyperekplexia.Frontiers in molecular neuroscience · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-pi interaction with the agonist, whereas in GABA(A) receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-pi interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC(50) value and the cation-pi binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-pi interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-pi interaction between Phe and a neurotransmitter.
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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.