{
  "abstract": "MBOAT2 suppresses ferroptosis independently of GPX4 and FSP1 by transferring monounsaturated acyl chains from acyl-CoA donors to lysophospholipid acceptors, but the structural basis of its catalytic cycle remains unclear. Here, we report the first cryo-EM structures of human MBOAT2, capturing endogenous and substrate-induced ligand-bound states. Unexpectedly, as-purified MBOAT2 contains a co-purified phospholipid-like density consistent with a retained product, together with a second density at a putative acyl-donor entry site. Oleoyl-CoA addition reduces the ordered product-like density and reveals donor density, whereas LPE addition increases local heterogeneity near the archway. The inactive H373A mutant contains endogenous donor- and acceptor-like densities along the two access pathways, consistent with substrate preloading. Together, these structures define the catalytic architecture of MBOAT2, support a product-retained, donor-primed working model, and provide templates for structure-guided ligand discovery.",
  "abstract_shown": true,
  "affiliations": [
    "UT Southwestern Medical Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "F. Liu"
    },
    {
      "name": "J. Li"
    },
    {
      "name": "W. Shin"
    },
    {
      "name": "J. Coria"
    },
    {
      "name": "L. Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/73qxd65n21rft.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.05.749645",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749645v1.full",
  "id": "73qxd65n21rft",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749645v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "2505|Enzyme Structure and Function"
    ]
  ],
  "openalex": "W7212056384",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749645v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/73qxd65n21rft.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:25Z",
      "native_id": "10.64898/2026.09.05.749645",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749645v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Structural insights into MBOAT2 catalysis, product retention, and ligand exchange",
  "title_text": "Structural insights into MBOAT2 catalysis, product retention, and ligand exchange",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:25Z",
  "url": "https://research.draconitic.com/paper/73qxd65n21rft",
  "venue": "bioRxiv",
  "versions": []
}