ArticleScience advances2022
Gating choreography and mechanism of the human proton-activated chloride channel ASOR.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Platelet-Collagen Interactions in Hemostatic Mechanisms.Advanced healthcare materials · 2026Review
- Conformational Fingerprints Underlying Thermal Modulation of PAC/TMEM206 Gating.International journal of molecular sciences · 2026Article
- Proton-activated chloride channel 1 is essential for innate host defense against bacterial sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PAC regulates endo-, and exocytosis, and lysosomal-mitochondrial stress signaling in human mast cells.Cell communication and signaling : CCS · 2026Article
- Structure of the human TWIK-2 potassium channel and its inhibition by pimozide.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alternative splicing regulates PACC1 function and promotes acidosis-induced cytotoxicity.Frontiers in cell and developmental biology · 2025Article
- Molecular insights into the inhibition of proton-activated chloride channel by transfer RNA.Cell research · 2024Article
- The plasma membrane inner leaflet PI(4,5)PNature communications · 2024Article
- Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles.Experimental & molecular medicine · 2024Review
- Knockout ofInternational journal of ophthalmology · 2024Article
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- A new polymodal gating model of the proton-activated chloride channel.PLoS biology · 2023Article
- Review
- Recent advances in membrane mimetics for membrane protein research.Biochemical Society transactions · 2023Review
- Article
- Identification of the Acid-Sensitive Site Critical for Chloral Hydrate (CH) Activation of the Proton-Activated Chloride Channel.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Molecular mechanism underlying desensitization of the proton-activated chloride channel PAC.eLife · 2022Article
- The roles of two extracellular loops in proton sensing and permeation in human Otop1 proton channel.Communications biology · 2022Article
- Molecular determinants of pH sensing in the proton-activated chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The proton-activated chloride channel ASOR (TMEM206/PAC) permeates anions across cellular membranes in response to acidification, thereby enhancing acid-induced cell death and regulating endocytosis. The molecular mechanisms of pH-dependent control are not understood, in part because structural information for an activated conformation of ASOR is lacking. Here, we reconstitute function from purified protein and present a 3.1-Å-resolution cryo-electron microscopy structure of human ASOR at acidic pH in an activated conformation. The work contextualizes a previous acidic pH structure as a desensitized conformation. Combined with electrophysiological studies and high-resolution structures of resting and desensitized states, the work reveals mechanisms of proton sensing and ion pore gating. Clusters of extracellular acidic residues function as pH sensors and coalesce when protonated. Ensuing conformational changes induce metamorphosis of transmembrane helices to fashion an ion conduction pathway unique to the activated conformation. The studies identify a new paradigm of channel gating in this ubiquitous ion channel.
Identifiers
What OpenQuestion holds
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.