{
  "abstract": "The ribosome biases the conformations sampled by nascent polypeptide chains along folding pathways towards biologically active states. A hallmark of the co-translational folding (coTF) of many proteins are highly stable folding intermediates that are absent or only transiently populated off the ribosome, yet persist during translation well-beyond complete emergence of the domain from the ribosome exit tunnel. Intermediates are important for folding fidelity; however, their structures have remained elusive. Here, we have structurally characterised two coTF intermediates of an immunoglobulin-like domain by developing comprehensive 19 F NMR analyses using chemical shifts, paramagnetic relaxation enhancement (PRE), and protein engineering. We integrated these experimental data with extensive molecular dynamics (MD) simulations to obtain atomistic structures of the folding intermediates on the ribosome. The resulting intermediate structures are distinguished by native-like folds initiated from either their N-or C-termini, and reveal parallel folding pathways, which are structurally conserved within the protein domain family, in contrast to their in vitro refolding mechanisms. By redirecting proteins to fold along hierarchical, parallel routes, the ribosome may promote efficient folding by avoiding kinetic traps, and regulate nascent chain assembly and targeting by auxiliary factors to maintain cellular proteostasis.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK",
    "Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland",
    "Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London, London, UK",
    "Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK. j.christodoulou@ucl.ac.uk",
    "School of Natural Sciences, Birkbeck College, London, UK. j.christodoulou@ucl.ac.uk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sammy H. S. Chan",
      "orcid": "0000-0003-1156-1818"
    },
    {
      "affs": [
        0
      ],
      "name": "Julian O. Streit",
      "orcid": "0000-0001-6114-3636"
    },
    {
      "affs": [
        1,
        0
      ],
      "name": "Tomasz Włodarski",
      "orcid": "0000-0001-6498-334X"
    },
    {
      "affs": [
        0
      ],
      "name": "Alkistis N. Mitropoulou",
      "orcid": "0000-0002-1319-1294"
    },
    {
      "affs": [
        0
      ],
      "name": "Anaïs M. E. Cassaignau",
      "orcid": "0000-0003-3963-082X"
    },
    {
      "affs": [
        0
      ],
      "name": "Ivana V. Bukvin",
      "orcid": "0000-0003-1429-9245"
    },
    {
      "affs": [
        2,
        0
      ],
      "name": "Christopher A. Waudby",
      "orcid": "0000-0001-7810-3753"
    },
    {
      "affs": [
        0
      ],
      "name": "Lisa D. Cabrita",
      "orcid": "0000-0003-2963-8078"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "John C. Christodoulou",
      "orcid": "0000-0002-6710-3843"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0gd821n1ge0cv.bib",
  "cited_by": 10,
  "doi": "10.1038/s41594-026-01814-7",
  "fulltext_url": null,
  "id": "0gd821n1ge0cv",
  "issns": [
    "1545-9985",
    "1545-9993"
  ],
  "landing_url": "https://doi.org/10.1038/s41594-026-01814-7",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W4409355279",
  "pdf_url": null,
  "pmcid": "PMC13275320",
  "pmid": "42304112",
  "published": "2026-06-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/0gd821n1ge0cv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W4409355279",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41594-026-01814-7"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structures of protein folding intermediates on the ribosome",
  "title_text": "Structures of protein folding intermediates on the ribosome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:07Z",
  "url": "https://research.draconitic.com/paper/0gd821n1ge0cv",
  "venue": "Nature Structural & Molecular Biology",
  "versions": []
}