Kraus A et al. 2021, High-resolution structure and strain comparison of infectious mammalian prions (Mol Cell 81(21):4540-4551.e6)

This 2021 Molecular Cell paper reports a near-atomic cryo-electron microscopy structure of the core of fibrils taken from the brains of animals infected with the hamster 263K prion strain, and compares its shape with fibrils of the aRML mouse strain. The fibrils are built from stacked prion protein molecules, one per layer, held in parallel and in register, with sugar chains and lipid anchors pointing out from the core. It is a structural biology milestone for what the atlas calls strain biology: it gives a physical picture of why different prion strains can behave differently. It is not a diagnostic, therapeutic or clinical study. Reading depth: the Europe PMC and Crossref records (including an abstract summary) were opened; the publisher full text was not accessible (HTTP 403) and PubMed returned only a cookie notice, so no full read is claimed. Information only, not medical advice.

Key facts

  • Bibliographic record verified: ten authors from Allison Kraus to Byron Caughey, Molecular Cell volume 81, issue 21, pages 4540-4551.e6, DOI 10.1016/j.molcel.2021.08.011, PMID 34433091.
  • The structure is of the core of brain-derived, fully infectious 263K prion fibrils, determined by cryo-electron microscopy to near-atomic resolution.
  • The fibrils have parallel, in-register beta sheets, with each prion protein monomer contributing one rung to the fibril core.
  • N-linked sugar chains and the glycolipid anchor of the protein project outward from the fibril core rather than being buried in it.
  • Comparison with the aRML mouse strain showed substantial differences in fibril morphology; the abstract summary notes that both strains have an asymmetric cross-section without paired protofilaments.
  • The authors link the findings to prion propagation, strain differences, species barriers and membrane-associated pathogenesis, and suggest relevance to other disease-related amyloids.
  • The first listed affiliation is a pathology department at Case Western Reserve University; the last author is Byron Caughey, an existing atlas person. The record lists no grants.
  • The paper is not in PubMed Central; Crossref licence data indicate the version of record becomes open access under an Elsevier licence from 2022-11-04 after a 368 day embargo (not tested).
  • Follow-on cryo-EM structures appeared in 2022: an anchorless RML structure (Hoyt et al., 3.0 A) and a wild-type RML structure (Manka et al., 2.7 A), both reporting an in-register parallel beta-sheet core resembling 263K with strain-specific differences.
  • Europe PMC lists 80 cryo-EM and prion hits for RML or 263K; later titles include fibrils from deer with chronic wasting disease (2024) and a review of ex vivo prion structures co-authored by Kraus and Caughey (2022).

Timeline

  1. 2021Published online 25 August in Molecular Cell (Crossref record created 24 August).
  2. 2021Appeared in print, volume 81 issue 21 (1 November).
  3. 2022Two follow-on cryo-EM structures of RML mouse prion fibrils published together in Nature Communications on 13 July (Hoyt et al., Manka et al.), both comparing with 263K.

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Last checked 1 November 2026

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