Abstract：
:Spongiform encephalopathies are believed to be transmitted by a unique mechanism involving self-propagating conformational conversion of prion protein into a misfolded form. Here we demonstrate that fundamental aspects of mammalian prion propagation, including the species barrier and strain diversity, can be reproduced in vitro in a seeded fibrillization of the recombinant prion protein variant Y145Stop. Our data show that species-specific substitution of a single amino acid in a critical region completely changes the seeding specificity of prion protein fibrils. Furthermore, we demonstrate that sequence-based barriers that prevent cross-seeding between proteins from different species can be bypassed, and new barriers established, by a template-induced adaptation process that leads to the emergence of new strains of prion fibrils. Although the seeding barriers observed in this study do not fully match those seen in animals, the present findings provide fundamental insight into mechanistic principles of these barriers at a molecular level.
journal_name
Mol Celljournal_title
Molecular cellauthors
Vanik DL,Surewicz KA,Surewicz WKdoi
10.1016/s1097-2765(04)00155-8subject
Has Abstractpub_date
2004-04-09 00:00:00pages
139-45issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(04)00155-8journal_volume
14pub_type
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