{
  "abstract": "Ergosteryl-3β-O-L-aspartate synthase (ErdS) catalyzes tRNA-dependent aspartylation of ergosterol, a lipid essential for fungal cell membrane integrity. However, the functional significance of ergosteryl-aspartate and the molecular mechanisms underlying its synthesis remain unclear. Here, we show that ErdS localization is highly dynamic and that Erg-Asp is required for proper hyphal growth, sporulation, and spore germination, and likely influences stress tolerance. The cryo-electron microscopy structure of ErdS revealed an unprecedented sterol-binding pocket. In addition, the structures in complex with a non-hydrolyzable Asp-N-tRNAAsp show a tRNA-guided intramolecular aminoacyl transfer mechanism between two functional domains of the enzyme. The CCA end of tRNAAsp undergoes a large displacement to reach the aa-tRNA transfer active site, while the tRNA elbow is clamped by a long extension an N-terminal α-helix. The present structural and mutational analyses demonstrate that domain fusion, dynamic repositioning, and tRNA-mediated substrate handover underlie the multifunctional catalytic efficiency of ErdS and participates in Erg-Asp synthesis independently from protein synthesis. These findings elucidate the regulatory mechanism of tRNA-dependent sterol modification and provide insights into fungal membrane dynamics, highlighting potential targets for antifungal therapies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "Hanako Murayama"
    },
    {
      "name": "Nathaniel Yakobov"
    },
    {
      "name": "Nassira Mahmoudi"
    },
    {
      "name": "Sasha Legrosdidier"
    },
    {
      "name": "Nicolas Fournier"
    },
    {
      "name": "Solène Zuttion"
    },
    {
      "name": "Kanata Matsumoto"
    },
    {
      "name": "Michihiro Nishimura"
    },
    {
      "name": "Jingwei Ji"
    },
    {
      "name": "Bruno Senger"
    },
    {
      "name": "Laurence Huck"
    },
    {
      "name": "Howard Gamper"
    },
    {
      "name": "Yoshiaki Kise"
    },
    {
      "name": "Ralph Kleiner"
    },
    {
      "name": "Mathieu Frechin"
    },
    {
      "name": "Ya-Ming Hou"
    },
    {
      "name": "Hubert Becker"
    },
    {
      "name": "Yuzuru Itoh"
    },
    {
      "name": "Frédéric Fischer"
    },
    {
      "name": "Osamu Nureki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6s9ps7brs5fnf.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-73135-8",
  "fulltext_url": null,
  "id": "6s9ps7brs5fnf",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.science/hal-05780978v1",
  "language": "en",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "openalex",
      "1312|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7162644232",
  "pdf_url": "https://hal.science/hal-05780978/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-28",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/6s9ps7brs5fnf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "hal-05780978",
      "source": "hal",
      "url": "https://hal.science/hal-05780978v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA and protein synthesis mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structure of ergosteryl-aspartate synthase reveals how an entrapped tRNA is used like a prosthetic swinging arm in the synthesis of aminoacylated sterols",
  "title_text": "Structure of ergosteryl-aspartate synthase reveals how an entrapped tRNA is used like a prosthetic swinging arm in the synthesis of aminoacylated sterols",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/6s9ps7brs5fnf",
  "venue": "Nature Communications",
  "versions": []
}