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TitleA structural basis for prion strain diversity.
Journal, issue, pagesNat Chem Biol, Vol. 19, Issue 5, Page 607-613, Year 2023
Publish dateJan 16, 2023
AuthorsSzymon W Manka / Adam Wenborn / Jemma Betts / Susan Joiner / Helen R Saibil / John Collinge / Jonathan D F Wadsworth /
PubMed AbstractRecent cryogenic electron microscopy (cryo-EM) studies of infectious, ex vivo, prion fibrils from hamster 263K and mouse RML prion strains revealed a similar, parallel in-register intermolecular β- ...Recent cryogenic electron microscopy (cryo-EM) studies of infectious, ex vivo, prion fibrils from hamster 263K and mouse RML prion strains revealed a similar, parallel in-register intermolecular β-sheet (PIRIBS) amyloid architecture. Rungs of the fibrils are composed of individual prion protein (PrP) monomers that fold to create distinct N-terminal and C-terminal lobes. However, disparity in the hamster/mouse PrP sequence precludes understanding of how divergent prion strains emerge from an identical PrP substrate. In this study, we determined the near-atomic resolution cryo-EM structure of infectious, ex vivo mouse prion fibrils from the ME7 prion strain and compared this with the RML fibril structure. This structural comparison of two biologically distinct mouse-adapted prion strains suggests defined folding subdomains of PrP rungs and the way in which they are interrelated, providing a structural definition of intra-species prion strain-specific conformations.
External linksNat Chem Biol / PubMed:36646960 / PubMed Central
MethodsEM (helical sym.)
Resolution2.6 Å
Structure data

EMDB-15043, PDB-8a00:
Infectious mouse-adapted ME7 scrapie prion fibril purified from terminally-infected mouse brains
Method: EM (helical sym.) / Resolution: 2.6 Å

Source
  • mus musculus (house mouse)
  • house mouse (house mouse)
KeywordsPROTEIN FIBRIL / Prion

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