{
  "abstract": "G protein-coupled receptors (GPCRs) govern diverse cellular responses and are crucial drug targets. However, the sequence of structural events from G protein recognition to GDP release has remained elusive. Here, we leveraged the viral chemokine GPCR US28 to capture multiple activation states of the US28-Gq complex. Using cryo-electron microscopy and an engineered chemokine superagonist, we determined three distinct complex structures, capturing a GDP-bound Encounter state, the nucleotide-free Canonical state, and a putative intermediate bridging the two states, the Transition-to-Canonical state. These structures, along with simulations and functional data, provide high-resolution snapshots of a plausible G protein activation trajectory and support a stepwise conformational model for G protein activation. This activation cascade closely parallels mechanisms proposed for human GPCRs, suggesting a conserved GPCR signaling mechanism.",
  "abstract_shown": true,
  "affiliations": [
    "Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA USA",
    "Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA USA",
    "Department of Structural Biology, Stanford University School of Medicine, Stanford, CA USA",
    "Department of Pharmacology, Yale School of Medicine, New Haven, CT USA",
    "Cellular and Structural Physiology Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Bunkyo, Tokyo Japan",
    "Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan",
    "Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kevin M. Jude",
      "orcid": "0000-0002-3675-5136"
    },
    {
      "affs": [
        3
      ],
      "name": "Carl-Mikael Suomivuori",
      "orcid": "0000-0002-2445-8791"
    },
    {
      "affs": [
        1
      ],
      "name": "Deepa Waghray"
    },
    {
      "affs": [
        1
      ],
      "name": "Shoji Maeda",
      "orcid": "0000-0002-7762-9793"
    },
    {
      "affs": [
        4
      ],
      "name": "Yoshinori Fujiyoshi",
      "orcid": "0000-0002-8070-1493"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Asuka Inoue",
      "orcid": "0000-0003-0805-4049"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "K. Christopher Garcia",
      "orcid": "0000-0001-9273-0278"
    },
    {
      "affs": [
        4
      ],
      "name": "Naotaka Tsutsumi",
      "orcid": "0000-0002-3617-7145"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eksm2zvydrg5b.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78122-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714248/",
  "id": "eksm2zvydrg5b",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-78122-7",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7214550483",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78122-7_reference.pdf",
  "pmcid": "PMC13714248",
  "pmid": "42946734",
  "published": "2026-09-28",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/eksm2zvydrg5b.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:21:47Z",
      "native_id": "PMC13714248",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-78122-7"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structural basis of stepwise G protein activation by the viral chemokine receptor US28",
  "title_text": "Structural basis of stepwise G protein activation by the viral chemokine receptor US28",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:47Z",
  "url": "https://research.draconitic.com/paper/eksm2zvydrg5b",
  "venue": "Nature Communications",
  "versions": []
}