Structural Insights into Alternate Aggregated Prion Protein Forms

POLANO, maurizio
Bek, Alpan
BENETTİ, federico
lazzarino, marco
LEGNAME, giuseppe
The conversion of the cellular form of the prion protein (PrPC) to an abnormal, alternatively folded isoform (PrPSc) is the central event in prion diseases or transmissible spongiform encephalopathies. Recent studies have demonstrated de novo generation of murine prions from recombinant prion protein (recPrP) after inoculation into transgenic and wild-type mice. These so-called synthetic prions lead to novel prion diseases with unique neuropathological and biochemical features. Moreover, the use of recPrP in an amyloid seeding assay can specifically detect and amplify various strains of prions. We employed this assay in our experiments and analyzed in detail the morphology of aggregate structures produced under defined chemical constraints. Our results suggest that changes in the concentration of guanidine hydrochloride can lead to different kinetic traces in a typical thioflavin T(ThT) assay. Morphological and structural analysis of these aggregates by atomic force microscopy indicates a variation in the structure of the PrP molecular assemblies.


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Citation Formats
m. POLANO, A. Bek, f. BENETTİ, m. lazzarino, and g. LEGNAME, “Structural Insights into Alternate Aggregated Prion Protein Forms,” JOURNAL OF MOLECULAR BIOLOGY, pp. 1033–1042, 2009, Accessed: 00, 2020. [Online]. Available: