2.7 Å cryo-EM structure of ex vivo RML prion fibrils.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 07 2022
13 07 2022
Historique:
received:
06
01
2022
accepted:
27
04
2022
entrez:
13
7
2022
pubmed:
14
7
2022
medline:
16
7
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35831275
doi: 10.1038/s41467-022-30457-7
pii: 10.1038/s41467-022-30457-7
pmc: PMC9279362
doi:
Substances chimiques
Amyloid
0
Prion Proteins
0
Prions
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4004Subventions
Organisme : Wellcome Trust
ID : 206166/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U123192748
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U123160655
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/10
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106249/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U12316055
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202679/Z/16/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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