ArticleeLife2020
β11-12 linker isomerization governs acid-sensing ion channel desensitization and recovery.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- The multifaceted role of ASICs channels into the nervous system and their potential use as a therapeutic target for neuro-disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Identification, characterization, and structure-activity relationship of the ASIC3-selective peptide WRPRFa.Communications chemistry · 2025Article
- The bile acid-sensitive ion channel is gated by CaNature communications · 2025Article
- Structure and function of a broad-range thermal receptor in myriapods.Nature structural & molecular biology · 2025Article
- Molecular Insights into Single-Chain Lipid Modulation of Acid-Sensing Ion Channel 3.The journal of physical chemistry. B · 2024Article
- Mechanism of acid-sensing ion channel modulation by Hi1a.The Journal of general physiology · 2024Article
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Proline substitutions in the ASIC1 β11-12 linker slow desensitization.Biophysical journal · 2024Article
- A conserved peptide-binding pocket in HyNaC/ASIC ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Molecular Insights into Single Chain Lipid Modulation of Acid-Sensing Ion Channel 3.bioRxiv : the preprint server for biology · 2024Article
- Dynamic conformational changes of acid-sensing ion channels in different desensitizing conditions.Biophysical journal · 2024Article
- Revealing molecular determinants governing mambalgin-3 pharmacology at acid-sensing ion channel 1 variants.Cellular and molecular life sciences : CMLS · 2024Article
- Proline substitutions in the ASIC1 β11-12 linker slow desensitization.bioRxiv : the preprint server for biology · 2024Article
- Article
- Photomodulation of the ASIC1a acidic pocket destabilizes the open state.Protein science : a publication of the Protein Society · 2023Article
- Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention.Cell death discovery · 2023Review
- Probing the Effect of Acidosis on Tether-Mode Mechanotransduction of Proprioceptors.International journal of molecular sciences · 2023Article
- Genetically encoded crosslinkers to address protein-protein interactions.Protein science : a publication of the Protein Society · 2023Review
- Modulation of Slow Desensitization (Tachyphylaxis) of Acid-Sensing Ion Channel (ASIC)1a.Cellular and molecular neurobiology · 2023Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Acid-sensing ion channels (ASICs) are neuronal sodium-selective channels activated by reductions in extracellular pH. Structures of the three presumptive functional states, high-pH resting, low-pH desensitized, and toxin-stabilized open, have all been solved for chicken ASIC1. These structures, along with prior functional data, suggest that the isomerization or flipping of the β11-12 linker in the extracellular, ligand-binding domain is an integral component of the desensitization process. To test this, we combined fast perfusion electrophysiology, molecular dynamics simulations and state-dependent non-canonical amino acid cross-linking. We find that both desensitization and recovery can be accelerated by orders of magnitude by mutating resides in this linker or the surrounding region. Furthermore, desensitization can be suppressed by trapping the linker in the resting state, indicating that isomerization of the β11-12 linker is not merely a consequence of, but a necessity for the desensitization process in ASICs.
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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.