ArticleCommunications biology2021
Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Conformational plasticity of human acid-sensing ion channel 1a.Nature structural & molecular biology · 2026Article
- Acid-sensing ion channels in the vasculature: emerging roles in systemic and pulmonary circulations.Pflugers Archiv : European journal of physiology · 2026Review
- A conserved peptide-binding pocket in HyNaC/ASIC ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Progress on functions of intracellular domainZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Lycocasine A, aMolecules (Basel, Switzerland) · 2024Article
- The small molecule activator S3969 stimulates the epithelial sodium channel by interacting with a specific binding pocket in the channel's β-subunit.The Journal of biological chemistry · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- 4-(Azolyl)-Benzamidines as a Novel Chemotype for ASIC1a Inhibitors.International journal of molecular sciences · 2024Article
- Molecular determinants of ASIC1 modulation by divalent cations.Scientific reports · 2024Article
- Photomodulation of the ASIC1a acidic pocket destabilizes the open state.Protein science : a publication of the Protein Society · 2023Article
- Recent Advances in Computer-Aided Structure-Based Drug Design on Ion Channels.International journal of molecular sciences · 2023Review
- Analysis of residue-residue interactions in the structures of ASIC1a suggests possible gating mechanisms.European biophysics journal : EBJ · 2023Article
- Derivatives of 2-aminobenzimidazole potentiate ASIC open state with slow kinetics of activation and desensitization.Frontiers in physiology · 2023Article
- Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1.Communications biology · 2021Article
- Neurodegenerative Disease: What Potential Therapeutic Role of Acid-Sensing Ion Channels?Frontiers in cellular neuroscience · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid-sensing ion channels (ASICs) are proton-gated cation channels critical for neuronal functions. Studies of ASIC1, a major ASIC isoform and proton sensor, have identified acidic pocket, an extracellular region enriched in acidic residues, as a key participant in channel gating. While binding to this region by the venom peptide psalmotoxin modulates channel gating, molecular and structural mechanisms of ASIC gating modulation by small molecules are poorly understood. Here, combining functional, crystallographic, computational and mutational approaches, we show that two structurally distinct small molecules potently and allosterically inhibit channel activation and desensitization by binding at the acidic pocket and stabilizing the closed state of rat/chicken ASIC1. Our work identifies a previously unidentified binding site, elucidates a molecular mechanism of small molecule modulation of ASIC gating, and demonstrates directly the structural basis of such modulation, providing mechanistic and structural insight into ASIC gating, modulation and therapeutic targeting.
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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.