NR AVZG
AU Vasan,S.; Mong,P.Y.; Grossman,A.
TI Interaction of prion protein with small highly structured RNAs: detection and characterization of PrP-oligomers.
QU Neurochemical Research 2006 May; 31(5): 629-37
PT journal article
AB Conformational modification of normal prion protein (PrPc) to protease-resistant, beta-sheet rich, aggregates (PrPsc) is commonly accepted cause for prion diseases. On the other hand, several studies in recent years implicate soluble, protease-sensitive, oligomers of PrPc in neuronal damage. Previously, our group has shown that small, highly structured RNAs (shsRNAs), in conjunction with a serum factor, facilitated the conversion of hrPrP to a protease resistant, high molecular weight isoform. In the current study we demonstrate that shsRNAs, in the absence of the serum factor, generate soluble, protease-sensitive, and potentially toxic oligomers of ovrPrP. We have isolated a 500 kD oligomer by size exclusion chromatography of the reaction mixture and identified the accessible epitopes. The soluble PrP-oligomers were present in enhanced amounts in scrapie infected sheep brain and treating extracts of normal sheep brain with shsRNA resulted in oligomerization of endogenous PrP. Isolation, characterization of PrP-oligomers and their possible implication in prion diseases is discussed.
MH Animals; Base Sequence; Brain Chemistry; Endopeptidase K/metabolism; Enzyme-Linked Immunosorbent Assay/methods; Humans; Molecular Sequence Data; *Nucleic Acid Conformation; *Prions/chemistry/metabolism; *Protein Conformation; *RNA/chemistry/metabolism; Sheep
AD Q-RNA, Inc.,, 3960 Broadway, New York, NY 10032, USA
SP englisch
PO USA