ArticleThe Journal of biological chemistry2015
Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.
Article in The Journal of biological chemistry, 2015. 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, 38 citations in OpenAlex.
- A proton-gated channel identified in the centipede antenna.EMBO reports · 2025Article
- Molecular mechanisms and hotspots of pH sensing in ASIC1a revealed by computational and functional analysis.Communications biology · 2025Article
- Voltage-clamp fluorometry for advancing mechanistic understanding of ion channel mechanisms with a focus on acid-sensing ion channels.Biochemical Society transactions · 2024Review
- Revealing molecular determinants governing mambalgin-3 pharmacology at acid-sensing ion channel 1 variants.Cellular and molecular life sciences : CMLS · 2024Article
- Progress on functions of intracellular domainZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- 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
- Mutation of a conserved glutamine residue does not abolish desensitization of acid-sensing ion channel 1.The Journal of general physiology · 2021Article
- Article
- 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
- β11-12 linker isomerization governs acid-sensing ion channel desensitization and recovery.eLife · 2020Article
- Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis.Nature communications · 2020Article
- Structural and Functional Analysis of Gly212 Mutants Reveals the Importance of Intersubunit Interactions in ASIC1a Channel Function.Frontiers in molecular biosciences · 2020Article
- Shear force modulates the activity of acid-sensing ion channels at low pH or in the presence of non-proton ligands.Scientific reports · 2019Article
- Accelerated Current Decay Kinetics of a Rare Human Acid-Sensing ion Channel 1a Variant That Is Used in Many Studies as Wild Type.Frontiers in molecular neuroscience · 2019Article
- 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
- Gating mechanisms of acid-sensing ion channels.Nature · 2018Article
- ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway.International journal of molecular sciences · 2017Article
- 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
Corrections and comments
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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 (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.
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