{
  "id": 10531918,
  "title": "β-arrestin1 directly engages Gαs to sustain endosomal GPCR signaling",
  "url": "https://urgent.news/2026/09/28/arrestin1-directly-engages-g-s-to-sustain-endosomal-gpcr-signaling",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754863v1?rss=1"
  },
  "original_language": "en",
  "account": "Beta-arrestin1 directly interacts with Gs to maintain endosomal GPCR signaling. Unlike conventional beta-arrestins that terminate G protein-coupled receptor (GPCR) signaling, internalized receptors paradoxically sustain beta-arrestin1-dependent Gs/cAMP signaling from endosomes. The mechanism behind this counterintuitive behavior has been unclear, as previous studies showed receptor-beta-arrestin1-G protein assemblies positioned on opposite sides of the receptor without any contact between them. By investigating the parathyroid hormone type 1 receptor (PTH1R), researchers discovered that beta-arrestin1 binds Gs directly and engages its nucleotide-free state more strongly than it interacts with Gβγ. A cryo-electron microscopy structure of the agonist-bound PTH1R-beta-arrestin1-Gs complex at 3.1 Å resolution elucidates the interaction: beta-arrestin1 anchors to the phosphorylated receptor C-tail, leaving the transmembrane core free for Gs, and reorients to form a direct three-node interface. This interface clamps the Switch I, Switch II, and 3/β5 regions of Gs, with either side of the interface disruption leading to complex assembly abolishment and selective collapse of the internalization-dependent phase of cAMP production. Notably, the same interface governs beta-arrestin1-Gs coupling at the glucagon-like peptide-1 receptor. Consequently, beta-arrestin1 functions as a positive regulator, keeping Gs in a signaling-competent state, thereby providing a unifying structural basis for sustained endosomal GPCR signaling.",
  "summary": "{beta}-arrestins ({beta}arrs) are canonical terminators of G protein-coupled receptor (GPCR) signaling, yet internalized receptors paradoxically sustain {beta}arr-dependent Gs/cAMP signaling from endosomes. How a desensitizing scaffold can instead promote G protein activation has remained unresolved, because the receptor-{beta}arr-G protein assemblies described so far position the two transducers…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}