{
  "abstract": "Human alphacoronaviruses primarily infect the human upper respiratory tract, yet how temperature and receptor-binding coordinate viral spike (S) protein activation remains unclear. Using cryo-electron tomography and subtomogram averaging, we directly visualized the structural dynamics of S on human coronavirus 229E (HCoV-229E) virions under physiologically relevant temperatures and in the presence of the host receptor human aminopeptidase N (hAPN). We identified two prefusion S2 conformations, compact and loose, that interconvert reversibly by temperature, revealing intrinsic S2 “breathing” on virions. Receptor-binding domain (RBD)-up conformations are rare on apo virions but are promoted at 33°C and stabilized upon receptor binding. hAPN can bind bivalently to neighboring S, forming Gemini S-hAPN complexes. Receptor incubation further promotes conversion from prefusion to postfusion S, an effect enhanced at 33°C. Together, our results demonstrate an optimized temperature for the HCoV-229E viral fitness, and establish temperature and receptor binding as synergistic regulators of alphacoronavirus S activation. These findings provide a structural framework for understanding alphacoronavirus infectivity.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.",
    "Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, China.",
    "Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.",
    "Center for Life Sciences and Artificial Intelligence, Tsinghua University, Beijing 100084, China.",
    "School of Life Sciences, Tsinghua University, Beijing 100084, China.",
    "The Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Jiaming Liang",
      "orcid": "0000-0001-6622-2085"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Cheng Peng",
      "orcid": "0000-0001-6622-2085"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Ruixiao Tan",
      "orcid": "0000-0002-5963-1136"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Yutong Song",
      "orcid": "0000-0002-2206-9549"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Zheyuan Zhang",
      "orcid": "0000-0002-4146-0164"
    },
    {
      "affs": [
        1,
        4,
        5
      ],
      "name": "Jinfang Yu",
      "orcid": "0000-0002-2294-0752"
    },
    {
      "affs": [
        1,
        4,
        5
      ],
      "name": "Xinquan Wang"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Sai Li",
      "orcid": "0000-0002-9353-0355"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9nt4gssdv9ayk.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aef6880",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733899/",
  "id": "9nt4gssdv9ayk",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aef6880",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biomedicine and Life Sciences"
    ],
    [
      "heading",
      "Biophysics"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "SciAdv r-articles"
    ],
    [
      "heading",
      "Virology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": "PMC13733899",
  "pmid": "42981411",
  "published": "2026-11-04",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/9nt4gssdv9ayk.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T00:20:34Z",
      "native_id": "10.1126/sciadv.aef6880",
      "source": "feed-science",
      "url": "https://www.science.org/doi/abs/10.1126/sciadv.aef6880"
    },
    {
      "first_seen": "2026-11-08T12:23:35Z",
      "native_id": "PMC13733899",
      "source": "pmc",
      "url": "https://doi.org/10.1126/sciadv.aef6880"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Biophysics",
      "subfield": "biophysics"
    },
    {
      "field": "biology",
      "origin": "heading:Virology",
      "subfield": "microbiology"
    }
  ],
  "title": "On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike",
  "title_text": "On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:35Z",
  "url": "https://research.draconitic.com/paper/9nt4gssdv9ayk",
  "venue": "Science Advances",
  "versions": []
}