Manka SW et al. 2022, 2.7 A cryo-EM structure of ex vivo RML prion fibrils (Nat Commun 13:4004, PMID 35831275, doi 10.1038/s41467-022-30457-7)

This Nature Communications paper reports a 2.7 angstrom cryo-EM structure of the PrP fibrils in infectious prion material from mice carrying the RML mouse-adapted scrapie strain. It comes from the MRC Prion Unit at UCL (Institute of Prion Diseases), with Helen Saibil of Birkbeck as a co-author and John Collinge and Jonathan Wadsworth as senior authors. The fibril core is a single PrP molecule per rung stacked in a parallel, in-register beta-sheet, folded into two staggered lobes, and the fold resembles the earlier hamster 263K structure while differing in the C-terminal lobe. A companion paper from NIAID Rocky Mountain Laboratories solved a closely similar fold for anchorless RML the same day. Information only, summary level; no handling methods are given here. Read depth: open-access full text read through a summarising fetch, about 91 percent of the page.

Key facts

  • Citation verified: Nat Commun 13(1):4004, electronic publication 13 July 2022, DOI 10.1038/s41467-022-30457-7, PMID 35831275, PMCID PMC9279362, CC BY open access. The queued citation was correct.
  • Authors are Szymon W. Manka, Wenjuan Zhang, Adam Wenborn, Jemma Betts, Susan Joiner, Helen R. Saibil, John Collinge and Jonathan D. F. Wadsworth; funding came from the Wellcome Trust and the Medical Research Council.
  • The paper was received on 6 January 2022 and accepted on 27 April 2022.
  • Most fibrils in the images were single protofilaments, with paired protofilaments about one in ten; older negative-stain work had been read as mostly paired fibres.
  • The ordered core spans about PrP residues 94 to 225, with one PrP molecule per rung in a parallel in-register beta-sheet arrangement.
  • The core has two staggered lobes: an N-terminal lobe with a double hairpin and a C-terminal lobe with a single hairpin held by a disulphide bond; the N-linked glycans and GPI anchor project from the C-terminal lobe.
  • The fold is broadly like the 263K hamster fibril, but the C-terminal lobes differ and the 263K fibril has a tighter helical twist; the authors say this may reflect mouse versus hamster sequence or strain-specific templating, and testing it needs other strains on one sequence.
  • Data were deposited as EMD-13989 (map), PDB 7QIG (model) and EMPIAR-10992 (raw data).
  • The Hoyt et al. companion (Nat Commun 13:4005) reports a 3.0 A structure of anchorless RML, residues 93 to 230, from NIAID Rocky Mountain Laboratories and Case Western Reserve; it calls the Manka structure highly similar and concludes that glycans and the GPI anchor do not substantially change the core fold.

Timeline

  1. 2022Manka et al. manuscript received by Nature Communications.
  2. 2022Accepted (the Hoyt companion was accepted the same day).
  3. 2022Published online together with the Hoyt anchorless RML paper (Nat Commun 13:4004 and 13:4005).

People

Last checked 1 November 2026

Sources for this page