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Title | A structural basis for prion strain diversity. |
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Journal, issue, pages | Nat Chem Biol, Vol. 19, Issue 5, Page 607-613, Year 2023 |
Publish date | Jan 16, 2023 |
Authors | Szymon W Manka / Adam Wenborn / Jemma Betts / Susan Joiner / Helen R Saibil / John Collinge / Jonathan D F Wadsworth / |
PubMed Abstract | 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- ...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 links | Nat Chem Biol / PubMed:36646960 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 2.6 Å |
Structure data | EMDB-15043, PDB-8a00: |
Source |
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Keywords | PROTEIN FIBRIL / Prion |