Protease-sensitive scrapie prion protein in aggregates of heterogeneous sizes.

Abstract:

:The pathological prion protein PrP(Sc) is the only known component of the infectious prion. In cells infected with prions, PrP(Sc) is formed posttranslationally by the refolding of the benign cell surface glycoprotein PrP(C) into an aberrant conformation. The two PrP isoforms possess very different properties, as PrP(Sc) has a protease-resistant core, forms very large amyloidic aggregates in detergents, and is only weakly immunoreactive in its native form. We now show that prion-infected rodent brains and cultured cells contain previously unrecognized protease-sensitive PrP(Sc) varieties. In both ionic (Sarkosyl) and nonionic (n-octyl beta-D-glucopyranoside) detergents, the novel protease-sensitive PrP(Sc) species formed aggregates as small as 600 kDa, as measured by gel filtration. The denaturation dependence of PrP(Sc) immunoreactivity correlated with the size of the aggregate. The small PrP(Sc) aggregates described here are consistent with the previous demonstration of scrapie infectivity in brain fractions with a sedimentation coefficient as small as 40 S [Prusiner et al. (1980) J. Neurochem. 35, 574-582]. Our results demonstrate for the first time that prion-infected tissues contain protease-sensitive PrP(Sc) molecules that form low MW aggregates. Whether these new PrP(Sc) species play a role in the biogenesis or the pathogenesis of prions remains to be established.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Tzaban S,Friedlander G,Schonberger O,Horonchik L,Yedidia Y,Shaked G,Gabizon R,Taraboulos A

doi

10.1021/bi025958g

subject

Has Abstract

pub_date

2002-10-22 00:00:00

pages

12868-75

issue

42

eissn

0006-2960

issn

1520-4995

pii

bi025958g

journal_volume

41

pub_type

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