ArticlePLoS biology2017
Full mutational mapping of titratable residues helps to identify proton-sensors involved in the control of channel gating in the Gloeobacter violaceus pentameric ligand-gated ion channel.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 28 citations in OpenAlex.
- Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation.Nature communications · 2025Article
- Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cryo-EM structures of prokaryotic ligand-gated ion channel GLIC provide insights into gating in a lipid environment.Nature communications · 2024Article
- Short-chain mono-carboxylates as negative modulators of allosteric transitions in Gloeobacter violaceus ligand-gated ion channel, and impact of a pre-β5 strand (Loop Ω) double mutation on crotonate, not butyrate effect.Physiological reports · 2024Article
- Evolutionary conservation of Zinc-Activated Channel (ZAC) functionality in mammals: a range of mammalian ZACs assemble into cell surface-expressed functional receptors.Frontiers in molecular biosciences · 2023Article
- β subunits of GABACommunications biology · 2022Article
- Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC).Biochemical pharmacology · 2021Article
- Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel.eLife · 2021Article
- Article
- Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations.Life science alliance · 2021Article
- Coupling structure with function in acid-sensing ion channels: challenges in pursuit of proton sensors.The Journal of physiology · 2021Review
- Electrostatics, proton sensor, and networks governing the gating transition in GLIC, a proton-gated pentameric ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Gloeobacter violaceus ligand-gated ion channel (GLIC) has been extensively studied by X-ray crystallography and other biophysical techniques. This provided key insights into the general gating mechanism of pentameric ligand-gated ion channel (pLGIC) signal transduction. However, the GLIC is activated by lowering the pH and the location of its putative proton activation site(s) still remain(s) unknown. To this end, every Asp, Glu, and His residue was mutated individually or in combination and investigated by electrophysiology. In addition to the mutational analysis, key mutations were structurally resolved to address whether particular residues contribute to proton sensing, or alternatively to GLIC-gating, independently of the side chain protonation. The data show that multiple residues located below the orthosteric site, notably E26, D32, E35, and D122 in the lower part of the extracellular domain (ECD), along with E222, H235, E243, and H277 in the transmembrane domain (TMD), alter GLIC activation. D122 and H235 were found to also alter GLIC expression. E35 is identified as a key proton-sensing residue, whereby neutralization of its side chain carboxylate stabilizes the active state. Thus, proton activation occurs allosterically to the orthosteric site, at the level of multiple loci with a key contribution of the coupling interface between the ECD and TMD.
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