ArticleThe Journal of biological chemistry2011
Contributions of conserved residues at the gating interface of glycine receptors.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- A release of local subunit conformational heterogeneity underlies gating in a muscle nicotinic acetylcholine receptor.Nature communications · 2024Article
- Article
- 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
- 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
- Investigation of Congenital Myasthenia Reveals Functional Asymmetry of Invariant Acetylcholine Receptor (AChR) Cys-loop Aspartates.The Journal of biological chemistry · 2016Article
- Incorporation of Non-Canonical Amino Acids.Advances in experimental medicine and biology · 2015Review
- Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains.The Journal of general physiology · 2014Article
- The impact of human hyperekplexia mutations on glycine receptor structure and function.Molecular brain · 2014Review
- Propofol modulation of α1 glycine receptors does not require a structural transition at adjacent subunits that is crucial to agonist-induced activation.ACS chemical neuroscience · 2013Article
- Expression-dependent pharmacology of transient receptor potential vanilloid subtype 1 channels in Xenopus laevis oocytes.Channels (Austin, Tex.) · 2013Article
- Inhibitory glycine receptors: an update.The Journal of biological chemistry · 2012Review
- Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin.Frontiers in molecular neuroscience · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glycine receptors (GlyRs) are chloride channels that mediate fast inhibitory neurotransmission and are members of the pentameric ligand-gated ion channel (pLGIC) family. The interface between the ligand binding domain and the transmembrane domain of pLGICs has been proposed to be crucial for channel gating and is lined by a number of charged and aromatic side chains that are highly conserved among different pLGICs. However, little is known about specific interactions between these residues that are likely to be important for gating in α1 GlyRs. Here we use the introduction of cysteine pairs and the in vivo nonsense suppression method to incorporate unnatural amino acids to probe the electrostatic and hydrophobic contributions of five highly conserved side chains near the interface, Glu-53, Phe-145, Asp-148, Phe-187, and Arg-218. Our results suggest a salt bridge between Asp-148 in loop 7 and Arg-218 in the pre-M1 domain that is crucial for channel gating. We further propose that Phe-145 and Phe-187 play important roles in stabilizing this interaction by providing a hydrophobic environment. In contrast to the equivalent residues in loop 2 of other pLGICs, the negative charge at Glu-53 α1 GlyRs is not crucial for normal channel function. These findings help decipher the GlyR gating pathway and show that distinct residue interaction patterns exist in different pLGICs. Furthermore, a salt bridge between Asp-148 and Arg-218 would provide a possible mechanistic explanation for the pathophysiologically relevant hyperekplexia, or startle disease, mutant Arg-218 → Gln.
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