NR ASJY
AU Jones,E.M.; Surewicz,W.K.
TI Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids
QU Cell 2005 Apr 8; 121(1): 63-72
PT journal article
AB 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.
MH Amyloid/*chemistry/genetics/ultrastructure; Animals; Humans; Microscopy, Atomic Force; Mutation/*genetics; Prions/*chemistry/genetics/ultrastructure; Protein Conformation; Recombinant Proteins/*chemistry/genetics/ultrastructure; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Species Specificity; Spectroscopy, Fourier Transform Infrared
AD Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
SP englisch
PO USA