Fibrils of the hamster prion peptide (sHaPrP, sequence 108-144) were prepared in an acidic solution, and their structure was solved by cryogenic electron microscopy with a resolution of 2.23 Å based on the gold-standard Fourier shell correlation (FSC) curve. The fibril has a novel architecture that has never been found in other amyloid fibrils. Each fibril is assembled by four protofilaments (PFs) and has an ordered water channel in the center. Each protofilament contains three β-strands (125-130, 133-135, and 138-141) arranged in an "R"-shaped construct. The structural data indicate that these three β-strand segments are the most amyloidogenic region of the prion peptide/protein and might be the site of nucleation during fibrillization under conditions without denaturants.
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http://dx.doi.org/10.1021/jacs.2c05479 | DOI Listing |
mSphere
December 2024
Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
Inhalation of prions into the nasal cavity is an efficient route of infection. Following inhalation of infectious prions, animals develop disease with a similar incubation period compared with per os exposure, but with greater efficiency. To identify the reason for this increased efficiency, we identified neural structures that uniquely innervate the nasal cavity and neural structures known to mediate neuroinvasion following oral infection and used immunohistochemistry to determine the temporal and spatial accumulation of prions from hamster tissue sections containing cell bodies and axons at 2-week intervals following prion exposure.
View Article and Find Full Text PDFmBio
November 2024
Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
JAMA Neurol
December 2024
National Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
FEBS J
November 2024
Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
J Hosp Infect
December 2024
Molecular Virology Immunology Unit, Université Paris-Saclay, INRAE, UVSQ, Jouy-en-Josas, France. Electronic address:
Validation of prion inactivation processes for medical devices relies on in-vivo experimental protocols. However, bioassays are costly, long (1-2 years) and ethically disputable. Additionally, results obtained with one prion strain - for example, 263K (hamster-adapted strain originating from sheep scrapie) - cannot be easily extrapolated to relevant human prion strains, further questioning the utility of bioassays.
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