{
  "abstract": "G protein-coupled receptors (GPCRs) are cell surface integral membrane proteins that transduce environmental, hormonal and neurotransmitter molecular signals into intracellular responses. Here we studied a class D1 fungal receptor, Ste2, an obligate dimer that couples two G proteins per dimer and show that coupling of the second G protein has an 18-fold higher affinity than coupling of the first. The molecular mechanism uncovered suggests that coupling of the first G protein to one protomer stabilizes the adjacent protomer in an active conformation with a pre-formed G protein coupling site, thus increasing the affinity for coupling of the second G protein. Protomer-based stabilization of an adjacent protomer in a unique conformational state within a dimer may represent a general mechanism by which oligomerization alters GPCR pharmacology.",
  "abstract_shown": true,
  "affiliations": [
    "MRC LMB Cambridge, UK"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "V. Velazhahan"
    },
    {
      "name": "J. Manning"
    },
    {
      "name": "N. Ma"
    },
    {
      "name": "H. D. Taylor"
    },
    {
      "name": "S. Shrestha"
    },
    {
      "name": "Q. Chen"
    },
    {
      "name": "Y. Ren"
    },
    {
      "name": "S. H. McLaughlin"
    },
    {
      "name": "A. Leung"
    },
    {
      "name": "S. Bar"
    },
    {
      "name": "M. Martin"
    },
    {
      "name": "S. Blanchard"
    },
    {
      "name": "W. B. Asher"
    },
    {
      "name": "J. B. Kelley"
    },
    {
      "name": "H. Dohlman"
    },
    {
      "name": "N. Vaidehi"
    },
    {
      "name": "J. Javitch"
    },
    {
      "affs": [
        0
      ],
      "name": "C. G. Tate"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0j7y4yg7tsrva.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.764869",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764869v1.full",
  "id": "0j7y4yg7tsrva",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764869v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764869v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0j7y4yg7tsrva.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:23:15Z",
      "native_id": "10.64898/2026.11.06.764869",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764869v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "Positive cooperativity enhances coupling of a second G protein to a GPCR dimer",
  "title_text": "Positive cooperativity enhances coupling of a second G protein to a GPCR dimer",
  "type": "preprint",
  "updated_at": "2026-11-10T00:23:15Z",
  "url": "https://research.draconitic.com/paper/0j7y4yg7tsrva",
  "venue": "bioRxiv",
  "versions": []
}