{
  "abstract": "Activation of heterotrimeric G proteins by G-protein-coupled receptors (GPCRs) requires large-scale opening of the Gα α-helical domain (AHD) to expose the nucleotide-binding site and facilitate GDP-GTP exchange. Although orthosteric ligands are known to modulate GPCR conformation, how these effects propagate to the bound G protein remains unclear. Using single-molecule Förster resonance energy transfer imaging, we monitored AHD motions in Gi proteins coupled to the μ-opioid receptor across different ligand- and nucleotide-bound states. We find that receptor ligands differentially modulate these dynamics from a binding site over 70 Å away, with higher-efficacy agonists accelerating transitions to an open, low-nucleotide-affinity conformation. These data also capture transient AHD intermediates during nucleotide exchange and suggest that allosteric control over the G protein conformational states provides an additional mechanism for encoding opioid efficacy and signaling outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.",
    "Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.",
    "Department of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany.",
    "Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.",
    "Departments of Materials Science and Engineering, Chemical and Biomolecular Engineering, and Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.",
    "Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA.",
    "Departments of Physics, Energy Sciences, and Engineering, Stanford University, Stanford, CA, USA.",
    "Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA. kobilka@stanford.edu.",
    "Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA. rvshiv@stanford.edu.",
    "Aerys Biosciences, Palo Alto, CA, USA. rvshiv@stanford.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jonathan C Deutsch"
    },
    {
      "affs": [
        2
      ],
      "name": "Daniel Hilger",
      "orcid": "0000-0001-5179-1357"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "John Janetzko",
      "orcid": "0000-0003-1604-2515"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Charles M Schroeder",
      "orcid": "0000-0001-6023-2274"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Steven Chu"
    },
    {
      "affs": [
        7
      ],
      "name": "Brian K Kobilka",
      "orcid": "0000-0001-5958-3990"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Rabindra V Shivnaraine",
      "orcid": "0000-0002-1478-5422"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d7jgmrsf7f68t.bib",
  "cited_by": 1,
  "doi": "10.1038/s41594-026-01893-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13672048",
  "id": "d7jgmrsf7f68t",
  "issns": [
    "1545-9993",
    "1545-9985"
  ],
  "landing_url": "https://europepmc.org/article/MED/42870023",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7221593804",
  "pdf_url": "https://europepmc.org/articles/PMC13672048?pdf=render",
  "pmcid": "PMC13672048",
  "pmid": "42870023",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d7jgmrsf7f68t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42870023",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42870023"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Ligand-dependent G protein dynamics underlying opioid efficacy.",
  "title_text": "Ligand-dependent G protein dynamics underlying opioid efficacy.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/d7jgmrsf7f68t",
  "venue": "Nature structural & molecular biology",
  "versions": []
}