{
  "abstract": "Protein phosphatases counterbalance kinases by dephosphorylating phospho-proteins to regulate signaling pathways. But unlike kinases, their shallow catalytic groove has limited selectivity for the phospho-peptide motifs. Phosphatases such as protein phosphatase-1 (PP1) recognize their substrates through short linear motifs (SLiMs) within intrinsically disordered regions, yet the mechanism of SLiM-mediated recruitment remains unclear. We developed an intrinsically disordered phospho-protein substrate to enable quantitative modelling of tethered PP1 catalysis by varying SLiM affinity and distance. We show that a PP1-binding SLiM linked to a phospho-peptide by a flexible spacer is sufficient to enhance dephosphorylation. Dephosphorylation occurs most efficiently at a spacing of 20-30 residues, in agreement with predictions from theoretical polymer models. Low micromolar dissociation constants are most efficient for dephosphorylation, which can be modelled numerically as a trade-off between substrate binding and substrate inhibition. Bivalent SLiMs enhance or decrease catalysis depending on the combined affinity. Together, these results define a quantitative and generalizable framework for how linear motifs direct dephosphorylation by PP1.",
  "abstract_shown": true,
  "affiliations": [
    "Aarhus University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "E. S. Lande"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Kjaergaard"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2aztymmj461e8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.09.750541",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750541v1.full",
  "id": "2aztymmj461e8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750541v1",
  "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",
      "biophysics"
    ],
    [
      "openalex",
      "1312|Protein Tyrosine Phosphatases"
    ]
  ],
  "openalex": "W7212309876",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750541v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2aztymmj461e8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:15Z",
      "native_id": "10.64898/2026.09.09.750541",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750541v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Affinity and distance dependence of SLiM-mediated dephosphorylation by protein phosphatase 1",
  "title_text": "Affinity and distance dependence of SLiM-mediated dephosphorylation by protein phosphatase 1",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:15Z",
  "url": "https://research.draconitic.com/paper/2aztymmj461e8",
  "venue": "bioRxiv",
  "versions": []
}