Cryo-EM structure of a human prion fibril with a hydrophobic, protease-resistant core
- 13 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 27 (5), 417-423
- https://doi.org/10.1038/s41594-020-0403-y
Abstract
Self-templating assemblies of the human prion protein are clinically associated with transmissible spongiform encephalopathies. Here we present the cryo-EM structure of a denaturant- and protease-resistant fibril formed in vitro spontaneously by a 9.7-kDa unglycosylated fragment of the human prion protein. This human prion fibril contains two protofilaments intertwined with screw symmetry and linked by a tightly packed hydrophobic interface. Each protofilament consists of an extended beta arch formed by residues 106 to 145 of the prion protein, a hydrophobic and highly fibrillogenic disease-associated segment. Such structures of prion polymorphs serve as blueprints on which to evaluate the potential impact of sequence variants on prion disease.Keywords
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