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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Glynn C,Sawaya MR,Ge P,Gallagher-Jones M,Short CW,Bowman R,Apostol M,Zhou ZH,Eisenberg DS,Rodriguez JAdoi
10.1038/s41594-020-0403-ysubject
Has Abstractpub_date
2020-05-01 00:00:00pages
417-423issue
5eissn
1545-9993issn
1545-9985pii
10.1038/s41594-020-0403-yjournal_volume
27pub_type
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