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TitleCryo-EM structure of a natural prion: chronic wasting disease fibrils from deer.
Journal, issue, pagesActa Neuropathol, Vol. 148, Issue 1, Page 56, Year 2024
Publish dateOct 24, 2024
AuthorsParvez Alam / Forrest Hoyt / Efrosini Artikis / Jakub Soukup / Andrew G Hughson / Cindi L Schwartz / Kent Barbian / Michael W Miller / Brent Race / Byron Caughey /
PubMed AbstractChronic 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 ...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.
External linksActa Neuropathol / PubMed:39448454 / PubMed Central
MethodsEM (helical sym.)
Resolution2.8 Å
Structure data

47020

9dmy

EMDB-47020, PDB-9dmy:
Chronic wasting disease prion fibril
Method: EM (helical sym.) / Resolution: 2.8 Å

47021

9dmz

EMDB-47021, PDB-9dmz:
Glycosylated chronic wasting disease prion fibril
Method: EM (helical sym.) / Resolution: 2.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • odocoileus virginianus (white-tailed deer)
KeywordsPROTEIN FIBRIL / Prion / Chronic Wasting Disease / Deer / Fibril / GPI-anchor / PrP / Infectious / Amyloid / Brain-derived / ex vivo / Prion strain / Glycosylation

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