Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids - PubMed (original) (raw)

. 2005 Apr 8;121(1):63-72.

doi: 10.1016/j.cell.2005.01.034.

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Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids

Eric M Jones et al. Cell. 2005.

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Abstract

Spongiform encephalopathies are believed to be transmitted by self-perpetuating conformational conversion of the prion protein. It was shown recently that fundamental aspects of mammalian prion propagation can be reproduced in vitro in a seeded fibrillization of the recombinant prion protein variant Y145Stop (PrP23-144). Here we demonstrate that PrP23-144 amyloids from different species adopt distinct secondary structures and morphologies, and that these structural differences are controlled by one or two residues in a critical region. These sequence-specific structural characteristics correlate strictly with the seeding specificity of amyloid fibrils. However, cross-seeding of PrP23-144 from one species with preformed fibrils from another species may overcome natural sequence-based structural preferences, resulting in a new amyloid strain that inherits the secondary structure and morphology of the template. These data provide direct biophysical evidence that protein conformations are transmitted in PrP amyloid strains, establishing a foundation for a structural basis of mammalian prion transmission barriers.

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