{
  "abstract": "TDP-43 (TAR DNA-binding protein 43) is a 414-amino acid protein with a structured N-terminal domain (NTD), two RNA recognition motifs (RRM1 and RRM2), and a long disordered C-terminal low complexity domain (LCD). TDP-43 forms phase-separated condensates as part of its physiological function in RNA processing. However, aberrant TDP-43 condensation, changes in condensate material properties, and subsequent aggregation are linked to the development of neurodegenerative diseases. Using explicit-solvent, near-atomic resolution coarse-grained simulations we demonstrate how the interplay among different domains drives phase separation of the full-length protein.We directly capture how the secondary structure of a conserved helix in the LCD modulates phase separation, and follow the effect of phosphomimicking mutations on the condensation of full-length TDP-43. C-terminal phosphomimicking mutations rewire the interactions of the LCD by increasing solvation locally and enhancing Na+ binding to the LCD. Our simulations and in vitro experiments emphasize the importance of the aromatic residues in the LCD but also of N-terminal residues 1-101 including the NTD for full-length TDP-43 condensation. With a Go-type approach we capture not just conformational flexibility but also specific dimer formation through NTD-NTD interactions and how they modulate the phase behavior as well as the dynamic and interfacial properties of full-length TDP-43 condensates.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Biology, Institute of Molecular Physiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany; Institute of Molecular Biology (IMB), 55128 Ma"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "X. Ping"
    },
    {
      "name": "R. G. M. Badr"
    },
    {
      "name": "S. Hutten"
    },
    {
      "name": "X. Chen"
    },
    {
      "name": "L. Baltz"
    },
    {
      "name": "M. Yadav"
    },
    {
      "name": "J. S. Hoeppner"
    },
    {
      "name": "F. Schmid"
    },
    {
      "name": "D. Dormann"
    },
    {
      "affs": [
        0
      ],
      "name": "L. S. Stelzl"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/07qw3g13c910y.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.06.03.729912",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.03.729912v4.full",
  "id": "07qw3g13c910y",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.03.729912v4",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7163664030",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.06.03.729912v4.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/07qw3g13c910y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:24Z",
      "native_id": "10.64898/2026.06.03.729912",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.03.729912v4"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Multi-Domain Interplay Controls Full-Length TDP-43 Phase Separation and Condensate Dynamics",
  "title_text": "Multi-Domain Interplay Controls Full-Length TDP-43 Phase Separation and Condensate Dynamics",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:24Z",
  "url": "https://research.draconitic.com/paper/07qw3g13c910y",
  "venue": "bioRxiv",
  "versions": []
}