{
  "abstract": "Keratins are intermediate filament (IF) proteins expressed in various cell types, playing a crucial role in mechanical support and signaling pathways. Keratin 19 (K19) is predominantly found in gut epithelia and early embryonic ectoderm. K19 interacts with signaling proteins such as GSK3{beta} and 14-3-3 to participate in cell signaling pathways. However, details on the binding sites of these proteins on K19, and specific molecular mechanisms governing these interactions, are lacking. Additionally, the N-terminal head domains of IFs including K19 are considered intrinsically disordered regions (IDRs), and their atomic-resolution structures are unavailable. Using NMR spectroscopy, we obtained the first solution structures of K19 head domain peptides. Structural models involving phosphomimetic peptides suggest a phosphorylation-dependent conformational change in the K19 head domain. The phosphomimetic S35E substitution alters the conformation of the head domain, affecting its association with keratin filaments and K19-binding partners. NMR spectral changes indicate that the S35E substitution affects the association of the K19 head domain to K8/K19 filaments and GSK3{beta}, whereas no significant binding changes were observed with 14-3-3{zeta} and 14-3-3{sigma}. Cell-based analyses further showed that the S35E mutation altered keratin filament organization and reduced the proximity between K19 and GSK3{beta} in 293T cells, whereas no significant change was observed in the proximity between K19 and 14-3-3{sigma}. Our findings provide insight into the structure-function relationship of the head domains in IF proteins with direct implications for the assembly of filaments and their role in signal modulation.",
  "abstract_shown": true,
  "affiliations": [
    "Daegu Gyeongbuk Institute of Science and Technology (DGIST)"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Y. Ji"
    },
    {
      "name": "M. Jeong"
    },
    {
      "name": "J. Kim"
    },
    {
      "name": "J. Yeom"
    },
    {
      "name": "M. A. Han"
    },
    {
      "name": "C. Park"
    },
    {
      "affs": [
        0
      ],
      "name": "S.-H. Lee"
    },
    {
      "name": "E. Hong"
    },
    {
      "name": "Y. H. Ko"
    },
    {
      "name": "P. A. Coulombe"
    },
    {
      "name": "J. H. Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "C.-H. Lee"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4q25d1zssk1fj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.764774",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764774v1.full",
  "id": "4q25d1zssk1fj",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764774v1",
  "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/10.64898/2026.11.06.764774v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4q25d1zssk1fj.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:11Z",
      "native_id": "10.64898/2026.11.06.764774",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764774v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "Phosphorylation-dependent conformational change in the Keratin 19 head domain: Implications for filament assembly and binding to GSK3β and 14-3-3",
  "title_text": "Phosphorylation-dependent conformational change in the Keratin 19 head domain: Implications for filament assembly and binding to GSK3β and 14-3-3",
  "type": "preprint",
  "updated_at": "2026-11-09T12:21:11Z",
  "url": "https://research.draconitic.com/paper/4q25d1zssk1fj",
  "venue": "bioRxiv",
  "versions": []
}