ArticlePloS one2018
Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Conformational plasticity of human acid-sensing ion channel 1a.Nature structural & molecular biology · 2026Article
- The Isolated Thumb Domain of Acid-Sensing Ion Channels Forms a Minimal Folding Unit Enabling Ligand Binding Studies.Angewandte Chemie (International ed. in English) · 2026Article
- The bile acid-sensitive ion channel is gated by CaNature communications · 2025Article
- A conserved peptide-binding pocket in HyNaC/ASIC ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification of the modulatory CaOpen biology · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Molecular determinants of ASIC1 modulation by divalent cations.Scientific reports · 2024Article
- Probing the Proton-Gated ASIC Channels Using Tetraalkylammonium Ions.Biomolecules · 2023Article
- Photomodulation of the ASIC1a acidic pocket destabilizes the open state.Protein science : a publication of the Protein Society · 2023Article
- The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.The Journal of physiology · 2023Article
- Modulation of Slow Desensitization (Tachyphylaxis) of Acid-Sensing Ion Channel (ASIC)1a.Cellular and molecular neurobiology · 2023Article
- Analysis of residue-residue interactions in the structures of ASIC1a suggests possible gating mechanisms.European biophysics journal : EBJ · 2023Article
- Calcium regulates acid-sensing ion channel 3 activation by competing with protons in the channel pore and at an allosteric binding site.Open biology · 2022Article
- Review
- Galvani Offset Potential and Constant-pH Simulations of Membrane Proteins.The journal of physical chemistry. B · 2022Article
- Accessibility of ENaC extracellular domain central core residues.The Journal of biological chemistry · 2022Article
- An arginine residue in the outer segment of hASIC1a TM1 affects both proton affinity and channel desensitization.The Journal of general physiology · 2021Article
- Article
- Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1.Communications biology · 2021Article
- DEG/ENaC Ion Channels in the Function of the Nervous System: From Worm to Man.Advances in experimental medicine and biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Acid sensing ion channels (ASICs) are proton-gated ion channels that are members of the degenerin/epithelial sodium channel superfamily and are expressed throughout central and peripheral nervous systems. ASICs have been implicated in multiple physiological processes and are subject to numerous forms of endogenous and exogenous regulation that include modulation by Ca2+ and Cl- ions. However, the mapping of ion binding sites as well as a structure-based understanding of the mechanisms underlying ionic modulation of ASICs have remained elusive. Here we present ion binding sites of chicken ASIC1a in resting and desensitized states at high and low pH, respectively, determined by anomalous diffraction x-ray crystallography. The acidic pocket serves as a nexus for divalent cation binding at both low and high pH, while we observe divalent cation binding within the central vestibule on the resting channel at high pH only. Moreover, neutralization of residues positioned to coordinate divalent cations via individual and combined Glu to Gln substitutions reduced, but did not extinguish, modulation of proton-dependent gating by Ca2+. Additionally, we demonstrate that anion binding at the canonical thumb domain site is state-dependent and present a previously undetected anion site at the mouth of the extracellular fenestrations on the resting channel. Our results map anion and cation sites on ASICs across multiple functional states, informing possible mechanisms of modulation and providing a blueprint for the design of therapeutics targeting ASICs.
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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.