{
  "abstract": "Parasitic nematodes infect billions of humans and livestock worldwide, causing major health and economic burdens, while the spread of anthelmintic resistance threatens current control strategies. A critical step in parasite infection is the resumption of development of infective third-stage larvae (iL3) upon host entry, a process controlled by the nuclear receptor DAF-12. Activation of DAF-12 by dafachronic acids promotes developmental progression and reproductive maturation, making this receptor an attractive therapeutic target. However, the molecular mechanisms governing DAF-12 activation, particularly transcriptional coactivator recruitment, remain poorly understood. Here, we combined biophysical, cellular, structural, and bioinformatic approaches to investigate coactivator recognition by DAF-12 from the parasitic nematodes Brugia malayi and Haemonchus contortus. Crystal structures of ligand-bound DAF-12 ligand-binding domains in complex with coactivator-derived peptides reveal conserved features of ligand-dependent coactivator recruitment shared with mammalian nuclear receptors. In addition, we uncover previously unrecognized interaction features, including motif-specific contacts that extend beyond the canonical LXXLL binding mode of coactivators and distinct patterns of DAF-12 conservation across nematode clades. Structure-guided analyses redefine the interaction motif of the only described parasite-specific coactivator DIP-1 and suggest novel candidate motifs for DAF-12-interacting proteins. Together, these findings establish the structural basis of coactivator binding to nematode DAF-12 and provide mechanistic insight into the transcriptional regulation underlying parasite development. These results expand current understanding of nuclear receptor signaling in parasitic nematodes and provide a framework for the future design of strategies aimed at disrupting DAF-12 activation as a potential antiparasitic approach.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Manon Mallet"
    },
    {
      "name": "Yéléna Martin"
    },
    {
      "name": "João E Carvalho"
    },
    {
      "name": "Eva Guchen"
    },
    {
      "name": "Remy Betous"
    },
    {
      "name": "Cherine Bechara"
    },
    {
      "name": "Anne Lespine"
    },
    {
      "name": "Michael Schubert"
    },
    {
      "name": "William Bourguet"
    },
    {
      "name": "Albane Le Maire"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/35dx37jpbq78c.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014073",
  "fulltext_url": null,
  "id": "35dx37jpbq78c",
  "issns": [
    "1553-7366",
    "1553-7374"
  ],
  "landing_url": "https://hal.science/hal-05701198v2",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "hal",
      "1.sdv.bc"
    ],
    [
      "hal",
      "1.sdv.mp"
    ],
    [
      "hal",
      "2.sdv.bbm.bs"
    ],
    [
      "hal",
      "2.sdv.mp.par"
    ],
    [
      "openalex",
      "3404|Helminth infection and control"
    ]
  ],
  "openalex": "W7169799001",
  "pdf_url": "https://hal.science/hal-05701198/document",
  "pmcid": null,
  "pmid": "42475386",
  "published": "2026-07-20",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/35dx37jpbq78c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "hal-05701198",
      "source": "hal",
      "url": "https://hal.science/hal-05701198v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.bs",
      "subfield": "structural-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.bc",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.mp",
      "subfield": "microbiology"
    }
  ],
  "title": "Structural and evolutionary insights into DAF-12 interactions with transcriptional coactivators in parasitic nematodes",
  "title_text": "Structural and evolutionary insights into DAF-12 interactions with transcriptional coactivators in parasitic nematodes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:35Z",
  "url": "https://research.draconitic.com/paper/35dx37jpbq78c",
  "venue": "PLoS Pathogens",
  "versions": []
}