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Cryo-EM structure of a human prion fibril with a hydrophobic, protease-resistant core.

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.

SUBMITTER: Glynn C

PROVIDER: S-EPMC7338044 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Cryo-EM structure of a human prion fibril with a hydrophobic, protease-resistant core.

Glynn Calina C Sawaya Michael R MR Ge Peng P Gallagher-Jones Marcus M Short Connor W CW Bowman Ronquiajah R Apostol Marcin M Zhou Z Hong ZH Eisenberg David S DS Rodriguez Jose A JA

Nature structural & molecular biology 20200413 5

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 f ...[more]

PMID: 32284600

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