{
  "abstract": "The endoplasmic reticulum (ER) forms specialized microdomains that organize autophagy, lipid droplet formation, and the repair of damaged lysosomes. The PI3P-binding protein DFCP1/ZFYVE1 marks these microdomains, raising the question as to whether and how one protein could define such a subcompartment. Here we determine the structure of full-length human DFCP1 bound to membranes by cryo-electron tomography and single-particle cryo-electron microscopy. DFCP1 assembles into a helical coat, built from tetramers that stack around a constricted membrane tube. Its ATPase domains form the organizing core of the helix, while its ER-targeting domains insert deeply into the outer leaflet, and its FYVE domains grip PI3P. Coarse-grained molecular dynamics simulations show that the coat does not simply follow the curvature of the membrane but acts as a barrier to lipid diffusion, almost completely blocking the movement of its cognate lipid PI3P past the filament and concentrating it beneath the coat. Point mutations that break the assembly, membrane-insertion or PI3P-binding interfaces each impair lysosomal repair in cells, and the assembly is also required for the focal recruitment of the lipid transporter VPS13C. We propose that DFCP1 collars fence off a specialized ER microdomain, so that locally made lipids can reach sites of repair rather than escaping into bulk ER.",
  "abstract_shown": true,
  "affiliations": [
    "UC Berkeley"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Z. Cui"
    },
    {
      "name": "K. Palacio-Rodriguez"
    },
    {
      "name": "E. Herrmann"
    },
    {
      "name": "A. Kourniotis"
    },
    {
      "name": "M. Radulovic"
    },
    {
      "name": "S. Pust"
    },
    {
      "name": "K. Tapia"
    },
    {
      "name": "C. Raiborg"
    },
    {
      "name": "G. Hummer"
    },
    {
      "name": "H. Stenmark"
    },
    {
      "affs": [
        0
      ],
      "name": "J. H. Hurley"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cp0fm7n7anhaf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.19.759623",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.759623v1.full",
  "id": "cp0fm7n7anhaf",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.759623v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1307|Cellular transport and secretion"
    ]
  ],
  "openalex": "W7223292375",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.759623v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cp0fm7n7anhaf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:20Z",
      "native_id": "10.64898/2026.10.19.759623",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.19.759623v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair",
  "title_text": "Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:20Z",
  "url": "https://research.draconitic.com/paper/cp0fm7n7anhaf",
  "venue": "bioRxiv",
  "versions": []
}