{
  "abstract": "Maintaining pH homoeostasis is essential for neuronal excitability and for regulating cerebrospinal fluid (CSF). The Na⁺-dependent Cl⁻/HCO₃⁻ exchanger, NCBE (SLC4A10), abundant in the choroid plexus, contributes to CSF pH control by mediating bicarbonate flux, yet its molecular mechanism has remained unclear. Here we report cryo-EM structures of human NCBE in multiple functional states, revealing conserved binding sites for Na⁺, Cl⁻, and HCO₃⁻, as well as an unexpected K⁺ site indicating relaxed cation selectivity. The inhibitor DIDS binds above the substrate cavity, locking NCBE in an outward-facing conformation and defining a subfamily-selective inhibitory mechanism. Functional assays and molecular dynamics simulations support the coordination of ions and the inhibitory effects. Comparison with an AlphaFold3-predicted inward-facing model suggests an elevator-like transport mechanism and delineates the conformational transitions in Na⁺-dependent HCO₃⁻ transporters. Together, these findings establish a structural framework for NCBE and offer insights into ion coupling and pharmacological modulation within the SLC4 family.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Peixin Sun",
      "orcid": "0009-0004-4177-8609"
    },
    {
      "name": "Xinmin Wang"
    },
    {
      "name": "Yang Huang"
    },
    {
      "name": "Jinlun Kylian Zhang",
      "orcid": "0009-0008-6635-0552"
    },
    {
      "name": "Xurui Shen",
      "orcid": "0009-0004-3005-7494"
    },
    {
      "name": "Anqi Dong"
    },
    {
      "name": "Shiliang Wang"
    },
    {
      "name": "Xiaojun Guo"
    },
    {
      "name": "Guoming Shi",
      "orcid": "0000-0003-3817-9117"
    },
    {
      "name": "Jing Ding",
      "orcid": "0000-0001-5135-4210"
    },
    {
      "name": "Yudan Chi",
      "orcid": "0000-0002-4566-3305"
    },
    {
      "name": "Hanting Yang",
      "orcid": "0000-0002-3383-2204"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2fgt5tmph1z74.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77504-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13724665",
  "id": "2fgt5tmph1z74",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-77504-1",
  "language": "eng",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Ion Transport and Channel Regulation"
    ]
  ],
  "openalex": "W7215093196",
  "pdf_url": "https://www.nature.com/articles/s41467-026-77504-1_reference.pdf",
  "pmcid": "PMC13724665",
  "pmid": "42967927",
  "published": "2026-10-01",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/2fgt5tmph1z74.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-77504-1",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-77504-1"
    },
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42967927",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42967927"
    },
    {
      "first_seen": "2026-11-04T12:23:12Z",
      "native_id": "PMC13724665",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-77504-1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ion Transport and Channel Regulation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Substrate coupling and inhibition in human Na+-dependent Cl−/HCO3− exchanger NCBE (SLC4A10)",
  "title_text": "Substrate coupling and inhibition in human Na+-dependent Cl−/HCO3− exchanger NCBE (SLC4A10)",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:05Z",
  "url": "https://research.draconitic.com/paper/2fgt5tmph1z74",
  "venue": "Nature Communications",
  "versions": []
}