{
  "abstract": "Orthoherpesviridae infect most humans for life and cause myriad diseases. These viruses distribute cell-entry functions among receptor-binding proteins such as gD, the conserved membrane fusogen gB, and the gH/gL heterodimer, which couples receptor engagement to gB activation. Here, we report cryoEM structures of HSV-2 gH/gL, including complexes with four antibody fragments, in distinct conformational states. Structural analysis suggests that these structures represent pre-activation and intermediate states rather than a post-activation state. Antibody binding appears to shift the gH/gL conformational equilibrium of gH/gL, either stabilizing the pre-activation state or promoting refolding into intermediate or post-activation-like states. Two regions – the N terminus and a domain H2 switch – adopt distinct conformations and may transmit the activating signal from gD to gB. We propose that receptor-bound gD displaces the gH N terminus, initiating allosteric rearrangements that culminate in switch refolding and may help release prefusion gB from an autoinhibited gH/gL-gB complex. Switch conservation suggests that this activation mechanism may be shared across Orthoherpesviridae . These findings uncover structural principles governing gH/gL-mediated activation of membrane fusion.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Gonzalo L. González-Del Pino",
      "orcid": "0000-0002-0365-8583"
    },
    {
      "name": "Richard M. Walsh",
      "orcid": "0000-0002-8939-8988"
    },
    {
      "name": "Chanyoung Lee",
      "orcid": "0000-0002-4102-6528"
    },
    {
      "name": "Hunter C. Russell"
    },
    {
      "name": "Doina Atanasiu"
    },
    {
      "name": "Tina M. Cairns"
    },
    {
      "name": "Wan Ting Saw"
    },
    {
      "name": "Gary H. Cohen",
      "orcid": "0000-0002-8581-8068"
    },
    {
      "name": "Ekaterina E. Heldwein",
      "orcid": "0000-0003-3113-6958"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6ggnqenjyh0fa.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78793-2",
  "fulltext_url": null,
  "id": "6ggnqenjyh0fa",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78793-2",
  "language": null,
  "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": [
    [
      "openalex",
      "2713|Herpesvirus Infections and Treatments"
    ]
  ],
  "openalex": "W7223911178",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78793-2_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/6ggnqenjyh0fa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "10.1038/s41467-026-78793-2",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78793-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Herpesvirus Infections and Treatments",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Distinct conformational states of HSV-2 gH/gL captured by cryoEM reveal structural principles governing fusion activation",
  "title_text": "Distinct conformational states of HSV-2 gH/gL captured by cryoEM reveal structural principles governing fusion activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/6ggnqenjyh0fa",
  "venue": "Nature Communications",
  "versions": []
}