{
  "abstract": "Biased agonism at the angiotensin II type 1 receptor (AT1R) offers a promising strategy for developing safer cardiovascular therapeutics. While beta-arrestin-biased agonism has been extensively investigated, G protein-biased signaling remains poorly understood. Here, we report structures of AT1R coupled to G protein and either the endogenous agonist angiotensin II (AngII) or the G protein-biased agonist TRV055. The ligands adopt similar overall poses, with coordinated rearrangements extending from the orthosteric pocket to the intracellular surface. The structures provide a detailed view of a TM7-centered microswitch network linking ligand recognition to G protein coupling. Functional analyses of peptide analogs identify the ligand's amino terminus as a key determinant of G protein bias, while mutagenesis of the microswitch network shifts AngII toward beta-arrestin-biased signaling and converts the G protein-biased agonist TRV055 into a beta-arrestin-biased ligand. These findings establish a framework for G protein-biased AT1R activation and provide mechanistic insight for the rational design of pathway-selective GPCR therapeutics.",
  "abstract_shown": true,
  "affiliations": [
    "Harvard Medical School"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "J. Liu"
    },
    {
      "name": "M. Skiba"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Kruse"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f48gxkw1c0pws.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.13.758900",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758900v1.full",
  "id": "f48gxkw1c0pws",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758900v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7221774463",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758900v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f48gxkw1c0pws.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:48Z",
      "native_id": "10.64898/2026.10.13.758900",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.13.758900v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structural Basis for Angiotensin II Type I Receptor G Protein-biased Signaling",
  "title_text": "Structural Basis for Angiotensin II Type I Receptor G Protein-biased Signaling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:48Z",
  "url": "https://research.draconitic.com/paper/f48gxkw1c0pws",
  "venue": "bioRxiv",
  "versions": []
}