7QIG

Infectious mouse-adapted RML scrapie prion fibril purified from terminally-infected mouse brains

Summary for 7QIG

• Entry DOI: 10.2210/pdb7qig/pdb
• EMDB information: 13989
• Descriptor: Major prion protein (1 entity in total)
• Functional Keywords: prion, amyloid, prp, prion protein, mouse rml scrapie strain, ex vivo prion, protein fibril
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 3
• Total formula weight: 45870.31

Authors

Manka, S.W.,Zhang, W.,Wenborn, A.,Betts, J.,Joiner, S.,Saibil, H.R.,Collinge, J.,Wadsworth, J.D.F. (deposition date: 2021-12-14, release date: 2022-07-27, Last modification date: 2025-07-09)

Primary citation

Manka, S.W.,Zhang, W.,Wenborn, A.,Betts, J.,Joiner, S.,Saibil, H.R.,Collinge, J.,Wadsworth, J.D.F.
2.7 angstrom cryo-EM structure of ex vivo RML prion fibrils.
Nat Commun, 13:4004-4004, 2022

PubMed Abstract: Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains.

PubMed: 35831275
DOI: 10.1038/s41467-022-30457-7

Experimental method

ELECTRON MICROSCOPY (2.7 Å)