ArticleThe Journal of biological chemistry2016
The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- 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
- Molecular mechanisms and hotspots of pH sensing in ASIC1a revealed by computational and functional analysis.Communications biology · 2025Article
- Mutagenesis of the Peptide Inhibitor of ASIC3 Channel Introduces Binding to Thumb Domain of ASIC1a but Reduces Analgesic Activity.Marine drugs · 2024Article
- Identification of the modulatory CaOpen biology · 2024Article
- Photomodulation of the ASIC1a acidic pocket destabilizes the open state.Protein science : a publication of the Protein Society · 2023Article
- Function and phylogeny support the independent evolution of an ASIC-like Deg/ENaC channel in the Placozoa.Communications biology · 2023Article
- Aromatic amino acids in the finger domain of the FMRFamide-gated NaPflugers Archiv : European journal of physiology · 2023Article
- Review
- Acid-sensing ion channels modulate bladder nociception.American journal of physiology. Renal physiology · 2021Article
- High-throughput characterization of photocrosslinker-bearing ion channel variants to map residues critical for function and pharmacology.PLoS biology · 2021Article
- 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
- Properties and Differential Expression of HFrontiers in physiology · 2021Review
- Molecular Investigation of Chicken Acid-Sensing Ion Channel 1 β11-12 Linker Isomerization and Channel Kinetics.Frontiers in cellular neuroscience · 2021Article
- Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.eLife · 2020Article
- Structural and Functional Analysis of Gly212 Mutants Reveals the Importance of Intersubunit Interactions in ASIC1a Channel Function.Frontiers in molecular biosciences · 2020Article
- Nociceptor Signalling through ion Channel Regulation via GPCRs.International journal of molecular sciences · 2019Review
- Article
- Thumb domains of the three epithelial NaThe 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
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Acid-sensing ion channels (ASICs) are cation-selective proton-gated channels expressed in neurons that participate in diverse physiological processes, including nociception, synaptic plasticity, learning, and memory. ASIC subunits contain intracellular N and C termini, two transmembrane domains that constitute the pore, and a large extracellular loop with defined domains termed the finger, β-ball, thumb, palm, and knuckle. Here we examined the contribution of the finger, β-ball, and thumb domains to activation and desensitization through the analysis of chimeras and the assessment of the effect of covalent modification of introduced Cys at the domain-domain interfaces. Our studies with ASIC1a-ASIC2a chimeras showed that swapping the thumb domain between subunits results in faster channel desensitization. Likewise, the covalent modification of Cys residues at selected positions in the β-ball-thumb interface accelerates the desensitization of the mutant channels. Studies of accessibility with thiol-reactive reagents revealed that the β-ball and thumb domains reside apart in the resting state but that they become closer to each other in response to extracellular acidification. We propose that the thumb domain moves upon continuous exposure to an acidic extracellular milieu, assisting with the closing of the pore during channel desensitization.
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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.