2.7 Å cryo-EM structure of ex vivo RML prion fibrils
Szymon W Manka1, Wenjuan Zhang1, Adam Wenborn1
1MRC Prion Unit at UCL, Institute of Prion Diseases, University College London, 33 Cleveland Street, London, W1W 7FF, UK.
Nature Communications
|July 13, 2022
Summary
Researchers reveal the near-atomic structure of prion protein (PrP) fibrils from RML prion-infected mice using cryo-EM. These amyloid fibrils show distinct protofilament arrangements, offering insights into prion strain diversity.
Area of Science:
- Structural Biology
- Neuroscience
- Biochemistry
Background:
- Mammalian prions are infectious agents composed of misfolded prion protein (PrP) that propagate as distinct strains.
- Understanding the structural basis of prion strains is crucial for deciphering their pathogenesis.
Purpose of the Study:
- To determine the near-atomic resolution structure of PrP fibrils from RML prion-infected mouse brains.
- To elucidate the structural features that may underlie prion strain diversity.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to analyze highly infectious prion rod preparations.
- Near-atomic resolution structural determination of PrP fibrils.
Main Results:
- Prion rods contain single-protofilament helical amyloid fibrils and twisted pairs of these protofilaments.
- The ordered core of each PrP monomer spans residues 94-225, forming two asymmetric lobes.
- N-linked glycans and GPI anchor project from the C-terminal lobe.
- The overall architecture is similar to 263K hamster prions but shows marked conformational variations.
Conclusions:
- The determined structure provides detailed insights into the molecular architecture of RML prion fibrils.
- Conformational variations in PrP fibrils may explain the existence of distinct prion strains.
- This structural information is vital for understanding prion propagation and strain diversity.
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