Cryo-EM structure of a natural prion: chronic wasting disease fibrils from deer.
Amyloid
Chronic wasting disease
Cryo-electron microscopy
Deer
Prion
Structure
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
16
09
2024
accepted:
04
10
2024
revised:
02
10
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
24
10
2024
Statut:
epublish
Résumé
Chronic wasting disease (CWD) is a widely distributed prion disease of cervids with implications for wildlife conservation and also for human and livestock health. The structures of infectious prions that cause CWD and other natural prion diseases of mammalian hosts have been poorly understood. Here we report a 2.8 Å resolution cryogenic electron microscopy-based structure of CWD prion fibrils from the brain of a naturally infected white-tailed deer expressing the most common wild-type PrP sequence. Like recently solved rodent-adapted scrapie prion fibrils, our atomic model of CWD fibrils contains single stacks of PrP molecules forming parallel in-register intermolecular β-sheets and intervening loops comprising major N- and C-terminal lobes within the fibril cross-section. However, CWD fibrils from a natural cervid host differ markedly from the rodent structures in many other features, including a ~ 180° twist in the relative orientation of the lobes. This CWD structure suggests mechanisms underlying the apparent CWD transmission barrier to humans and should facilitate more rational approaches to the development of CWD vaccines and therapeutics.
Identifiants
pubmed: 39448454
doi: 10.1007/s00401-024-02813-y
pii: 10.1007/s00401-024-02813-y
doi:
Substances chimiques
Prions
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
56Subventions
Organisme : National Institute of Allergy and Infectious Diseases
ID : ZIA-A1000580
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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