Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.

Disease-related prion protein, PrP(Sc), is classically distinguished from its normal cellular precursor, PrP(C), by its detergent insolubility and partial resistance to proteolysis. Molecular diagnosis of prion disease typically relies upon detection of protease-resistant fragments of PrP(Sc) using...

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Main Authors: Laura D'Castro, Adam Wenborn, Nathalie Gros, Susan Joiner, Sabrina Cronier, John Collinge, Jonathan D F Wadsworth
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-12-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0015679&type=printable
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author Laura D'Castro
Adam Wenborn
Nathalie Gros
Susan Joiner
Sabrina Cronier
John Collinge
Jonathan D F Wadsworth
author_facet Laura D'Castro
Adam Wenborn
Nathalie Gros
Susan Joiner
Sabrina Cronier
John Collinge
Jonathan D F Wadsworth
author_sort Laura D'Castro
collection DOAJ
description Disease-related prion protein, PrP(Sc), is classically distinguished from its normal cellular precursor, PrP(C), by its detergent insolubility and partial resistance to proteolysis. Molecular diagnosis of prion disease typically relies upon detection of protease-resistant fragments of PrP(Sc) using proteinase K, however it is now apparent that the majority of disease-related PrP and indeed prion infectivity may be destroyed by this treatment. Here we report that digestion of RML prion-infected mouse brain with pronase E, followed by precipitation with sodium phosphotungstic acid, eliminates the large majority of brain proteins, including PrP(C), while preserving >70% of infectious prion titre. This procedure now allows characterization of proteinase K-sensitive prions and investigation of their clinical relevance in human and animal prion disease without being confounded by contaminating PrP(C).
format Article
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publisher Public Library of Science (PLoS)
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series PLoS ONE
spelling doaj-art-b342d1c5b92d4a38a2135ea008355eed2025-08-20T03:19:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-12-01512e1567910.1371/journal.pone.0015679Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.Laura D'CastroAdam WenbornNathalie GrosSusan JoinerSabrina CronierJohn CollingeJonathan D F WadsworthDisease-related prion protein, PrP(Sc), is classically distinguished from its normal cellular precursor, PrP(C), by its detergent insolubility and partial resistance to proteolysis. Molecular diagnosis of prion disease typically relies upon detection of protease-resistant fragments of PrP(Sc) using proteinase K, however it is now apparent that the majority of disease-related PrP and indeed prion infectivity may be destroyed by this treatment. Here we report that digestion of RML prion-infected mouse brain with pronase E, followed by precipitation with sodium phosphotungstic acid, eliminates the large majority of brain proteins, including PrP(C), while preserving >70% of infectious prion titre. This procedure now allows characterization of proteinase K-sensitive prions and investigation of their clinical relevance in human and animal prion disease without being confounded by contaminating PrP(C).https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0015679&type=printable
spellingShingle Laura D'Castro
Adam Wenborn
Nathalie Gros
Susan Joiner
Sabrina Cronier
John Collinge
Jonathan D F Wadsworth
Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.
PLoS ONE
title Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.
title_full Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.
title_fullStr Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.
title_full_unstemmed Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.
title_short Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic acid.
title_sort isolation of proteinase k sensitive prions using pronase e and phosphotungstic acid
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0015679&type=printable
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