Hallinan GI et al. 2022, Cryo-EM structures of prion protein filaments from Gerstmann-Straussler-Scheinker disease (Acta Neuropathol 144(3):509-520, PMID 35819518, doi 10.1007/s00401-022-02461-0)

A structural biology paper from an Indiana University-led group (senior authors Ghetti and Vidal) that used cryo-electron microscopy to resolve the architecture of prion protein amyloid filaments taken from human brain in Gerstmann-Straussler-Scheinker disease (GSS), a genetic prion disease. It reports a previously undescribed spiral fold common to all filament types and discusses implications for imaging and therapy design. It is open access and the citation as queued was checked against Crossref and Europe PMC and found correct. Summary-level information only; the full text was read through a summarising fetch tool and the last part was not read.

Key facts

  • Citation verified: Hallinan GI and 14 co-authors, Acta Neuropathologica 144(3):509-520, DOI 10.1007/s00401-022-02461-0, PMID 35819518, PMCID PMC9381446; no correction to the scout citation was needed.
  • The paper is open access under a CC BY 4.0 licence.
  • The filaments came from brain tissue of two donors with GSS linked to the PRNP F198S variant, analysed in aggregate here; one sample gave three filament types, the other only the simplest.
  • The filaments are left-handed and made of two, three or four intertwined protofilaments, resolved at about 3.3, 5.5 and 3.1 angstroms respectively for the doublet, triplet and quadruplet forms.
  • All protofilaments share one spiral fold whose core spans residues 80 to 141 and contains nine short beta-strands, with a steric zipper between two strands and a Greek key arrangement between two others.
  • The authors note the ordered core is a truncated piece of the protein, with a less ordered outer region, unexplained surface densities, and a link to tau co-aggregation in this disease.
  • The authors propose the structures could help design PrP-specific imaging agents and therapeutic targets; this is their suggestion, not a demonstrated outcome.
  • Stated limitations: only two donors, possible extraction effects on which forms appear, some densities unresolved, and packing models for lower-resolution forms are hypothetical.
  • Work was funded by US National Institutes of Health grants and Indiana University.

Timeline

  1. 2022Manuscript received by Acta Neuropathologica (13 April).
  2. 2022Revised and accepted (23 June).
  3. 2022Published online (12 July); print issue September 2022.

Last checked 1 November 2026

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