Structural highlights
FunctionPublication Abstract from PubMedChronic 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 A 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 beta-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 degrees 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. Cryo-EM structure of a natural prion: chronic wasting disease fibrils from deer.,Alam P, Hoyt F, Artikis E, Soukup J, Hughson AG, Schwartz CL, Barbian K, Miller MW, Race B, Caughey B Acta Neuropathol. 2024 Oct 24;148(1):56. doi: 10.1007/s00401-024-02813-y. PMID:39448454[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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