{
  "id": 6378971,
  "title": "Structural insights into MBOAT2 catalysis, product retention, and ligand exchange",
  "url": "https://urgent.news/2026/09/08/structural-insights-into-mboat2-catalysis-product-retention-and",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-08T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749645v1?rss=1"
  },
  "original_language": "en",
  "account": "MBOAT2 is a protein that prevents ferroptosis without relying on GPX4 or FSP1. It achieves this by transferring monounsaturated acyl chains from acyl-CoA donors to lysophospholipid acceptors. However, the precise mechanism behind its catalytic process has remained enigmatic.\n\nTo unravel this mystery, researchers have now obtained the first cryo-EM structures of human MBOAT2. These structures showcase both endogenous and substrate-induced ligand-bound states. Surprisingly, the purified MBOAT2 protein shows a phospholipid-like density associated with a retained product, alongside another density at a potential acyl-donor entry site.\n\nWhen Oleoyl-CoA is added, the ordered product-like density decreases, and donor density becomes apparent. Conversely, when LPE (lysophospholipid equivalent) is introduced, local heterogeneity near the archway intensifies. Notably, the inactive H373A mutant exhibits endogenous donor- and acceptor-like densities along the two access pathways, suggesting substrate preloading.\n\nThese newly acquired structures elucidate the catalytic machinery of MBOAT2, substantiate the idea of product retention with a donor-primed working model, and offer templates for the guided development of potential ligands.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}