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

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

Research output: Contribution to journalArticlepeer-review

Abstract

One of the main characteristics of the transmissible isoform of the prion protein (PrPSc) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrPSc following Western blot or ELISA. More recently, researchers determined that there is a sizeable fraction of PrPSc that is sensitive to PK hydrolysis (sPrPSc). 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 sPrPSc versus the PK-resistant (rPrPSc) fractions of PrPSc and analyzed the biochemical characteristics of these fractions under conditions of limited proteolysis. Our results show that sPrPSc and rPrPSc 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 sPrPSc to the rPrPSc forms of PrPSc. Although the sPrPSc and rPrPSc 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.

Original languageEnglish (US)
Article numbere1002547
JournalPLoS pathogens
Volume8
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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