PK-sensitive PrP is infectious and shares basic structural features with PK-resistant PrP.

Autor: Gustavo Sajnani, Christopher J Silva, Adriana Ramos, Miguel A Pastrana, Bruce C Onisko, Melissa L Erickson, Elizabeth M Antaki, Irina Dynin, Ester Vázquez-Fernández, Christina J Sigurdson, J Mark Carter, Jesús R Requena
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS Pathogens, Vol 8, Iss 3, p e1002547 (2012)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1002547
Popis: One of the main characteristics of the transmissible isoform of the prion protein (PrP(Sc)) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrP(Sc) following Western blot or ELISA. More recently, researchers determined that there is a sizeable fraction of PrP(Sc) that is sensitive to PK hydrolysis (sPrP(Sc)). Our group has previously reported a method to isolate this fraction by centrifugation and showed that it has protein misfolding cyclic amplification (PMCA) converting activity. We compared the infectivity of the sPrP(Sc) versus the PK-resistant (rPrP(Sc)) fractions of PrP(Sc) and analyzed the biochemical characteristics of these fractions under conditions of limited proteolysis. Our results show that sPrP(Sc) and rPrP(Sc) fractions have comparable degrees of infectivity and that although they contain different sized multimers, these multimers share similar structural properties. Furthermore, the PK-sensitive fractions of two hamster strains, 263K and Drowsy (Dy), showed strain-dependent differences in the ratios of the sPrP(Sc) to the rPrP(Sc) forms of PrP(Sc). Although the sPrP(Sc) and rPrP(Sc) fractions have different resistance to PK-digestion, and have previously been shown to sediment differently, and have a different distribution of multimers, they share a common structure and phenotype.
Databáze: Directory of Open Access Journals
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