{
  "abstract": "Most proteins start to fold cotranslationally as they come off the ribosome. So far, studies of cotranslational folding have focused mainly on small, single-domain proteins. Here, we have used Force Profile Analysis to study the cotranslational folding of Firefly Luciferase, a complex 550-residue protein composed of an N-terminal domain (NTD) encompassing two split Rossmann folds (RF-1, RF-2) and a β-roll, and a flexibly attached C-terminal domain (CTD). The folding process is characterized by a quasi-continuous series of compaction/folding steps that generate intermediate-size pulling forces on the nascent chain, punctuated by a prominent high-force event that represents the folding of the RF-2 domain, and a few low-force instances that likely indicate the formation of distinct folding intermediates. Trigger Factor interacts extensively with the nascent chain when the central part of RF-2 and the early parts of the CTD are synthesized. Our analysis uncovers a cotranslational compaction/folding process that is rich in detail and not just a simple succession of a few distinct, cooperative folding transitions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.",
    "Department of Structural Biology, Stanford University, Palo Alto, CA, USA.",
    "Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. gunnar.von.heijne@dbb.su.se.",
    "Science for Life Laboratory Stockholm University, Box 1031, Solna, Sweden. gunnar.von.heijne@dbb.su.se.",
    "Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. ane.metola@dbb.su.se."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Spyridoula Mitsikosta",
      "orcid": "0009-0008-2387-0507"
    },
    {
      "affs": [
        0
      ],
      "name": "Justin M Westerfield"
    },
    {
      "affs": [
        1
      ],
      "name": "Fátima Pardo-Avila",
      "orcid": "0009-0002-9040-4684"
    },
    {
      "affs": [
        1
      ],
      "name": "Michael Levitt",
      "orcid": "0000-0002-8414-7397"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Gunnar von Heijne",
      "orcid": "0000-0002-4490-8569"
    },
    {
      "affs": [
        4
      ],
      "name": "Ane Metola",
      "orcid": "0000-0002-2885-7634"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4ex4xk7hga65c.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78090-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13639035",
  "id": "4ex4xk7hga65c",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78090-y",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7220411026",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78090-y.pdf",
  "pmcid": "PMC13639035",
  "pmid": "42834059",
  "published": "2026-10-05",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/4ex4xk7hga65c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-78090-y",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78090-y"
    },
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42834059",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42834059"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Quasi-continuous cotranslational compaction and folding of a multidomain protein",
  "title_text": "Quasi-continuous cotranslational compaction and folding of a multidomain protein",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/4ex4xk7hga65c",
  "venue": "Nature Communications",
  "versions": []
}