{
  "abstract": "Acid-sensing ion channels (ASICs) are typically activated by acidic environments and contribute to nociception and synaptic plasticity. ASIC1a is the most abundant subunit in the central nervous system and forms homomeric channels permeable to Na + and Ca 2+ , making it a compelling therapeutic target for acidotic pathologies including stroke and traumatic brain injury. However, a complete conformational library of human ASIC1a has yet to be described. Here we show that human ASIC1a adopts six major conformations, resolved by cryo-electron microscopy across a pH range between 8.5 and 5.7 and in the presence of a toxin agonist and a gating-modifying amino acid substitution. These major conformations establish linear transmembrane helices to be associated with an open state, delineate mechanistic differences between proton and toxin activation and demonstrate that desensitization involves unexpected conformational diversity in the transmembrane domain. Together, they provide a three-dimensional framework to integrate previous structure–function studies on ASIC.",
  "abstract_shown": true,
  "affiliations": [
    "Vollum Institute, Oregon Health and Science University, Portland, OR, USA",
    "Vollum Institute, Oregon Health & Science University, Portland, OR 97239",
    "Department of Biomedical and Clinical Sciences, Linköping University, Linkoping, Sweden",
    "Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark",
    "University of Copenhagen, Department of Drug Design and Pharmacology, Jagtvej 160, 100 Copenhagen, Denmark",
    "Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 9729",
    "Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA",
    "Vollum Institute, Oregon Health and Science University, Portland, OR, USA. bacongui@ohsu.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "James Cahill",
      "orcid": "0000-0003-0351-4384"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kimberly A. Hartfield",
      "orcid": "0000-0002-7290-5648"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Stephanie Andrea Heusser",
      "orcid": "0000-0003-3224-4547"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Nadine Ritter",
      "orcid": "0000-0003-2749-885X"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Mette Homann Poulsen"
    },
    {
      "affs": [
        6,
        4
      ],
      "name": "Craig Yoshioka"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Stephan Alexander Pless",
      "orcid": "0000-0001-6654-114X"
    },
    {
      "affs": [
        7
      ],
      "name": "Isabelle Baconguis",
      "orcid": "0000-0002-5440-2289"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/50q29m2qnh628.bib",
  "cited_by": 7,
  "doi": "10.1038/s41594-026-01845-0",
  "fulltext_url": null,
  "id": "50q29m2qnh628",
  "issns": [
    "1545-9985",
    "1545-9993"
  ],
  "landing_url": "https://doi.org/10.1038/s41594-026-01845-0",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2809|Ion Channels and Receptors"
    ]
  ],
  "openalex": "W4405308154",
  "pdf_url": "https://www.nature.com/articles/s41594-026-01845-0.pdf",
  "pmcid": "PMC11661276",
  "pmid": "39713315",
  "published": "2026-07-16",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/50q29m2qnh628.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T13:20:36Z",
      "native_id": "W4405308154",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41594-026-01845-0"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Ion Channels and Receptors",
      "subfield": "neuroscience"
    }
  ],
  "title": "Conformational plasticity of human acid-sensing ion channel 1a",
  "title_text": "Conformational plasticity of human acid-sensing ion channel 1a",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T13:21:09Z",
  "url": "https://research.draconitic.com/paper/50q29m2qnh628",
  "venue": "Nature Structural & Molecular Biology",
  "versions": []
}