{
  "abstract": "The direction of conformational coupling in a membrane protein, that is, which domain drives which, has been inaccessible to experiment. We recover this directivity from molecular dynamics (MD) of transmembrane-juxtamembrane (TM-JM) dimers of receptor tyrosine kinases EGFR and FGFR3. Coupling is detected with a Bayesian-network framework (CASCADE); its direction is measured with PERI (Phase-plane Estimation of Rotational Irreversibility), the net phase-plane circulation, validated on synthetic data and resolved at 0.1 ns. Direction is summarized as the TM[->]JM directed-mass fraction f+ (0.5 = balanced) via a hierarchical Bayesian model. The activating TM mutants EGFR L658Q and FGFR3 A391E are TM-JM (posterior probability 0.95 and 0.99); fluid wild-type EGFR leans the same way (0.93), in agreement with its experimentally reported constitutive activity in fluid but not ordered bilayers; the ligand-dependent ordered wild type is balanced (0.45); and an activating mutation raises the TM-JM bias above the ordered wild type with probability 0.94. The directivity thus tracks the measured activity state of the receptor, distinguishing signaling-competent from ligand-dependent RTK dimers by a property not apparent from structure alone.",
  "abstract_shown": true,
  "affiliations": [
    "Kyoto Pharmaceutical University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "T. Sato"
    },
    {
      "name": "H. Tamagaki-Asahina"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a9r97mcnehqbt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.22.727318",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.05.22.727318v2.full",
  "id": "a9r97mcnehqbt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.05.22.727318v2",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.05.22.727318v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a9r97mcnehqbt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:58Z",
      "native_id": "10.64898/2026.05.22.727318",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.05.22.727318v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "A directed TM->JM coupling in receptor tyrosine kinase dimers, set by activating mutations and the membrane environment",
  "title_text": "A directed TM->JM coupling in receptor tyrosine kinase dimers, set by activating mutations and the membrane environment",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:58Z",
  "url": "https://research.draconitic.com/paper/a9r97mcnehqbt",
  "venue": "bioRxiv",
  "versions": [
    {
      "doi": "10.1021/jacs.6c10487",
      "pid": null,
      "relation": "published-as",
      "title": null,
      "venue": null
    }
  ]
}