ArticleThe Journal of biological chemistry2012
Intramembrane proton binding site linked to activation of bacterial pentameric ion channel.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Correlating biological activity to thermo-structural analysis of the interaction of CTX with synthetic models of macrophage membranes.Scientific reports · 2021Article
- An allosteric link connecting the lipid-protein interface to the gating of the nicotinic acetylcholine receptor.Scientific reports · 2018Article
- Article
- A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.Neuropharmacology · 2017Article
- 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
- Pentameric ligand-gated ion channels exhibit distinct transmembrane domain archetypes for folding/expression and function.Scientific reports · 2017Article
- Article
- Signal Transduction at the Domain Interface of Prokaryotic Pentameric Ligand-Gated Ion Channels.PLoS biology · 2016Article
- Copper and protons directly activate the zinc-activated channel.Biochemical pharmacology · 2016Article
- The M4 Transmembrane α-Helix Contributes Differently to Both the Maturation and Function of Two Prokaryotic Pentameric Ligand-gated Ion Channels.The Journal of biological chemistry · 2015Article
- A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation.The Journal of general physiology · 2015Article
- Role of the Fourth Transmembrane α Helix in the Allosteric Modulation of Pentameric Ligand-Gated Ion Channels.Structure (London, England : 1993) · 2015Article
- Ethanol Modulation is Quantitatively Determined by the Transmembrane Domain of Human α1 Glycine Receptors.Alcoholism, clinical and experimental research · 2015Article
- Intramembrane aromatic interactions influence the lipid sensitivities of pentameric ligand-gated ion channels.The Journal of biological chemistry · 2015Article
- Mechanism of activation of the prokaryotic channel ELIC by propylamine: a single-channel study.The Journal of general physiology · 2015Article
- Structural requirements in the transmembrane domain of GLIC revealed by incorporation of noncanonical histidine analogs.Chemistry & biology · 2014Article
- 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
- Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Inter-residue coupling contributes to high-affinity subtype-selective binding of α-bungarotoxin to nicotinic receptors.The Biochemical journal · 2013Article
- Structural sensitivity of a prokaryotic pentameric ligand-gated ion channel to its membrane environment.The Journal of biological chemistry · 2013Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Prokaryotic orthologs of eukaryotic Cys-loop receptor channels recently emerged as structural and mechanistic surrogates to investigate this superfamily of intercellular signaling proteins. Here, we examine proton activation of the prokaryotic ortholog GLIC using patch clamp electrophysiology, mutagenesis, and molecular dynamics (MD) simulations. Whole-cell current recordings from human embryonic kidney (HEK) 293 cells expressing GLIC show half-maximal activation at pH 6, close to the pK(a) of histidine, implicating the three native His residues in proton sensing linked to activation. The mutation H235F abolishes proton activation, H277Y is without effect, and all nine mutations of His-127 prevent expression on the cell surface. In the GLIC crystal structure, His-235 on transmembrane (TM) α-helix 2, hydrogen bonds to the main chain carbonyl oxygen of Ile-259 on TM α-helix 3. MD simulations show that when His-235 is protonated, the hydrogen bond persists, and the channel remains in the open conformation, whereas when His-235 is deprotonated, the hydrogen bond dissociates, and the channel closes. Mutations of the proximal Tyr-263, which also links TM α-helices 2 and 3 via a hydrogen bond, alter proton sensitivity over a 1.5 pH unit range. MD simulations show that mutations of Tyr-263 alter the hydrogen bonding capacity of His-235. The overall findings show that His-235 in the TM region of GLIC is a novel proton binding site linked to channel activation.
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