In:
Protein Science, Wiley, Vol. 14, No. 5 ( 2005-05), p. 1222-1232
Abstract:
In recent studies, the amyloid form of recombinant prion protein (PrP) encompassing residues 89–230 (rPrP 89‐230) produced in vitro induced transmissible prion disease in mice. These studies showed that unlike “classical” PrP Sc produced in vivo, the amyloid fibrils generated in vitro were more proteinase‐K sensitive. Here we demonstrate that the amyloid form contains a proteinase K‐resistant core composed only of residues 152/153–230 and 162–230. The PK‐resistant fragments of the amyloid form are similar to those observed upon PK digestion of a minor subpopulation of PrP Sc recently identified in patients with sporadic Creutzfeldt‐Jakob disease (CJD). Remarkably, this core is sufficient for self‐propagating activity in vitro and preserves a β‐sheet‐rich fibrillar structure. Full‐length recombinant PrP 23‐230, however, generates two subpopulations of amyloid in vitro: One is similar to the minor subpopulation of PrP Sc , and the other to classical PrP Sc . Since no cellular factors or templates were used for generation of the amyloid fibrils in vitro, we speculate that formation of the subpopulation of PrP Sc with a short PK‐resistant C‐terminal region reflects an intrinsic property of PrP rather than the influence of cellular environments and/or cofactors. Our work significantly increases our understanding of the biochemical nature of prion infectious agents and provides a fundamental insight into the mechanisms of prions biogenesis.
Type of Medium:
Online Resource
ISSN:
0961-8368
,
1469-896X
DOI:
10.1110/ps.041186605
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2000025-X
SSG:
12
