{
  "abstract": "Frizzleds (FZDs) are class F G protein-coupled receptors (GPCRs) that primarily signal through Dishevelled (DVL) to initiate Wnt signalling, with evidence for context-specific coupling to heterotrimeric G proteins. Every FZD-G protein structure to date has been determined without an agonist, implying that agonist binding is not required for stable complex formation in vitro and directly contradicting the difficulty of demonstrating G protein coupling in cells. All these structures contain unassigned density between the receptor and the heterotrimeric G protein. From structures generated by single-particle cryo-electron microscopy (cryo-EM) of FZD7-Gs and FZD5-Gq, we identify this density as the detergent lauryl maltose neopentyl glycol (LMNG), which bridges the receptor and G protein to stabilise a weak, shallow interface. Absence of LMNG - in biochemical preparations and molecular dynamics simulations - destabilises the complex, showing that constitutive FZD-G protein engagement is intrinsically weak. The weak G protein coupling is governed by a conserved intracellular interface that when mutated differentially influences DVL and G protein signalling. Our findings show that LMNG has masked the instability of purified FZD-G protein complexes and provide the structural basis of FZDs as inherently weak G protein activators that are predisposed to DVL signalling.",
  "abstract_shown": true,
  "affiliations": [
    "WEHI"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "W. A. C. Burger"
    },
    {
      "name": "S. Das"
    },
    {
      "name": "H. Venugopal"
    },
    {
      "name": "A. S. Quinn"
    },
    {
      "name": "B. J. Williams-Noonan"
    },
    {
      "name": "L. L. L. Wong"
    },
    {
      "name": "T. T. Nguyen"
    },
    {
      "name": "J. R. Prendergast"
    },
    {
      "name": "N. S. Kirk"
    },
    {
      "name": "A. P. Leis"
    },
    {
      "name": "M. Dramicanin"
    },
    {
      "name": "T. Josephs"
    },
    {
      "name": "M. E. Call"
    },
    {
      "name": "G. Schulte"
    },
    {
      "name": "M. L. O'Mara"
    },
    {
      "name": "K. Huynh"
    },
    {
      "name": "A. Glukhova"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8mbr6pfms8zzb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.763784",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763784v1.full",
  "id": "8mbr6pfms8zzb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763784v1",
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763784v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8mbr6pfms8zzb.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:42Z",
      "native_id": "10.64898/2026.11.03.763784",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763784v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "Structural basis for inefficient G protein coupling by Frizzled receptors",
  "title_text": "Structural basis for inefficient G protein coupling by Frizzled receptors",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:54Z",
  "url": "https://research.draconitic.com/paper/8mbr6pfms8zzb",
  "venue": "bioRxiv",
  "versions": []
}