{
  "abstract": "M is the most abundant structural membrane protein in coronaviruses and is essential for the formation of infectious virus particles. SARS-CoV-2 M adopts two conformations, M short and M long , and regulated transition between states is hypothesized to coordinate viral assembly and budding. However, the factors that regulate M conformation and roles for each state are unknown. Here, we discover a direct M-sphingolipid interaction that controls M conformational dynamics and virus assembly. We show M binds Golgi-enriched anionic lipids including ceramide-1-phosphate (C1P). Molecular dynamics simulations show C1P interaction promotes a long to short transition and energetically stabilizes M short . Cryo-EM structures show C1P specifically binds M short at a conserved site bridging transmembrane and cytoplasmic regions. Disrupting M short -C1P interaction alters M subcellular localization, reduces interaction with Spike and E, and impairs subsequent virus-like particle cell entry. Together, these results show endogenous signaling lipids regulate M structure and support a model in which M short is stabilized in the early endomembrane system to organize other structural proteins prior to viral budding.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, The University of Chicago, Chicago, IL, USA",
    "The University of Chicago",
    "Department of Molecular & Cell Biology, Department of Neuroscience, California Institute for Quantitative Biology (QB3), Biophysics Graduate Program, University of California Berkeley, Berkeley, CA, USA",
    "University of California, Berkeley",
    "Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA",
    "Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, USA",
    "Purdue University",
    "Department of Chemistry, Pennsylvania State University, University Park, PA, USA",
    "University of Chicago",
    "University of California Berkeley",
    "Department of Biological Sciences, Purdue University, West Lafayette, IN, USA",
    "Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL, USA. gavoth@uchicago.edu",
    "Department of Chemistry, The University of Chicago, Chicago, IL, USA. gavoth@uchicago.edu",
    "Department of Molecular & Cell Biology, Department of Neuroscience, California Institute for Quantitative Biology (QB3), Biophysics Graduate Program, University of California Berkeley, Berkeley, CA, USA. brohawn@berkeley.edu",
    "Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA. rstaheli@purdue.edu",
    "Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, USA. rstaheli@purdue.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mandira Dutta"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Kimberly A. Dolan",
      "orcid": "0000-0002-9335-7791"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Souad Amiar",
      "orcid": "0000-0002-6117-0746"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Elijah J. Bass",
      "orcid": "0009-0005-1875-6134"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Rokaia Sultana",
      "orcid": "0009-0009-5468-646X"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Sean M. Braet",
      "orcid": "0000-0003-3782-2262"
    },
    {
      "affs": [
        4,
        5,
        9
      ],
      "name": "Karen Johanna Cárdenas-Martínez",
      "orcid": "0000-0002-7266-8769"
    },
    {
      "affs": [
        10,
        5,
        6
      ],
      "name": "Devika Sirohi",
      "orcid": "0000-0001-8601-6211"
    },
    {
      "affs": [
        2
      ],
      "name": "Ian K. Hicklin",
      "orcid": "0009-0009-0436-8981"
    },
    {
      "affs": [
        10,
        5
      ],
      "name": "Richard J. Kuhn",
      "orcid": "0000-0003-4148-1026"
    },
    {
      "affs": [
        7
      ],
      "name": "Ganesh S. Anand",
      "orcid": "0000-0001-8995-3067"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Gregory A. Voth",
      "orcid": "0000-0002-3267-6748"
    },
    {
      "affs": [
        13
      ],
      "name": "Stephen Graf Brohawn",
      "orcid": "0000-0001-6768-3406"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Robert Virgil Stahelin",
      "orcid": "0000-0001-5443-7863"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2kyw0at05phr5.bib",
  "cited_by": 14,
  "doi": "10.1038/s41467-026-75229-9",
  "fulltext_url": null,
  "id": "2kyw0at05phr5",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-75229-9",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
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  "openalex": "W4404061176",
  "pdf_url": null,
  "pmcid": "PMC11580925",
  "pmid": "39574576",
  "published": "2026-07-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/2kyw0at05phr5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:56Z",
      "native_id": "W4404061176",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-75229-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly",
  "title_text": "Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:51Z",
  "url": "https://research.draconitic.com/paper/2kyw0at05phr5",
  "venue": "Nature Communications",
  "versions": []
}