{
  "abstract": "The Smc5/6 complex (Smc5/6) preserves genome stability through ATP-dependent DNA organization, but the structural details that prime the complex for productive DNA engagement remain unknown. Here, we combine cryo-electron microscopy and conformational heterogeneity analysis to define the pre-catalytic activation pathway of Smc5/6. We show that in the absence of ATP and DNA, Smc5/6 exists as a heterogeneous conformational ensemble composed predominantly of two conformations termed Bridge and Cross. In the presence of DNA alone, Smc5/6 adopts a Juxtaposed conformation that brings the ATPase heads into proximity, aligning them for nucleotide engagement. With both ATP and DNA associated, Smc5/6 establishes an Engaged architecture, within which DNA stabilizes its head-associated binding cavity through local remodeling of the complex. Conformational heterogeneity analyses suggest a continuous structural transition between the Cross and Juxtaposed states, while anisotropic network modeling identifies the Bridge-Cross-Juxtaposed-Engaged sequence as the mechanically favored pathway connecting the four experimentally observed conformations. Together, these findings support a pre-catalytic conformational pathway for Smc5/6 activation and provide a structural framework for understanding how conformational heterogeneity gives rise to an activation-competent motor state.",
  "abstract_shown": true,
  "affiliations": [
    "Max Planck Institute of Biophysics"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "J. S. K. Wong"
    },
    {
      "name": "M. S. Loke"
    },
    {
      "name": "B. Pradhan"
    },
    {
      "name": "T. Kanno"
    },
    {
      "name": "C. Björkegren"
    },
    {
      "affs": [
        0
      ],
      "name": "E. Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/atvp209652t41.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.757879",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757879v1.full",
  "id": "atvp209652t41",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757879v1",
  "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",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7221528211",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757879v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/atvp209652t41.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:20Z",
      "native_id": "10.64898/2026.10.09.757879",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757879v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Pre-catalytic activation pathway of the Smc5/6 complex",
  "title_text": "Pre-catalytic activation pathway of the Smc5/6 complex",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:20Z",
  "url": "https://research.draconitic.com/paper/atvp209652t41",
  "venue": "bioRxiv",
  "versions": []
}