ArticleThe Journal of biological chemistry2013
Proton-mediated conformational changes in an acid-sensing ion channel.
Article in The Journal of biological chemistry, 2013. 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, 32 citations in OpenAlex.
- Molecular mechanisms and hotspots of pH sensing in ASIC1a revealed by computational and functional analysis.Communications biology · 2025Article
- Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.Signal transduction and targeted therapy · 2024Article
- Photomodulation of the ASIC1a acidic pocket destabilizes the open state.Protein science : a publication of the Protein Society · 2023Article
- Analysis of residue-residue interactions in the structures of ASIC1a suggests possible gating mechanisms.European biophysics journal : EBJ · 2023Article
- An arginine residue in the outer segment of hASIC1a TM1 affects both proton affinity and channel desensitization.The Journal of general physiology · 2021Article
- Coupling structure with function in acid-sensing ion channels: challenges in pursuit of proton sensors.The Journal of physiology · 2021Review
- Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.eLife · 2020Article
- The structural arrangement at intersubunit interfaces in homomeric kainate receptors.Scientific reports · 2019Article
- Gating mechanisms of acid-sensing ion channels.Nature · 2018Article
- Mapping allosteric linkage to channel gating by extracellular domains in the human epithelial sodium channel.The Journal of biological chemistry · 2018Article
- Cryo-EM structure of the ASIC1a-mambalgin-1 complex reveals that the peptide toxin mambalgin-1 inhibits acid-sensing ion channels through an unusual allosteric effect.Cell discovery · 2018Article
- Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization.The Journal of biological chemistry · 2016Article
- Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a.British journal of pharmacology · 2015Article
- Luminescence resonance energy transfer to study conformational changes in membrane proteins expressed in mammalian cells.Journal of visualized experiments : JoVE · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid-sensing ion channels are cation channels activated by external protons and play roles in nociception, synaptic transmission, and the physiopathology of ischemic stroke. Using luminescence resonance energy transfer (LRET), we show that upon proton binding, there is a conformational change that increases LRET efficiency between the probes at the thumb and finger subdomains in the extracellular domain of acid-sensing ion channels. Additionally, we show that this conformational change is lost upon mutating Asp-238, Glu-239, and Asp-260, which line the finger domains, to alanines. Electrophysiological studies showed that the single mutant D260A shifted the EC50 by 0.2 pH units, the double mutant D238A/E239A shifted the EC50 by 2.5 pH units, and the triple mutant D238A/E239A/D260A exhibited no response to protons despite surface expression. The LRET experiments on D238A/E239A/D260A showed no changes in LRET efficiency upon reduction in pH from 8 to 6. The LRET and electrophysiological studies thus suggest that the three carboxylates, two of which are involved in carboxyl/carboxylate interactions, are essential for proton-induced conformational changes in the extracellular domain, which in turn are necessary for receptor activation.
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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.