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PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc)
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 de...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291653/ https://www.ncbi.nlm.nih.gov/pubmed/22396643 http://dx.doi.org/10.1371/journal.ppat.1002547 |
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author | Sajnani, Gustavo Silva, Christopher J. Ramos, Adriana Pastrana, Miguel A. Onisko, Bruce C. Erickson, Melissa L. Antaki, Elizabeth M. Dynin, Irina Vázquez-Fernández, Ester Sigurdson, Christina J. Carter, J. Mark Requena, Jesús R. |
author_facet | Sajnani, Gustavo Silva, Christopher J. Ramos, Adriana Pastrana, Miguel A. Onisko, Bruce C. Erickson, Melissa L. Antaki, Elizabeth M. Dynin, Irina Vázquez-Fernández, Ester Sigurdson, Christina J. Carter, J. Mark Requena, Jesús R. |
author_sort | Sajnani, Gustavo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3291653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32916532012-03-06 PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc) Sajnani, Gustavo Silva, Christopher J. Ramos, Adriana Pastrana, Miguel A. Onisko, Bruce C. Erickson, Melissa L. Antaki, Elizabeth M. Dynin, Irina Vázquez-Fernández, Ester Sigurdson, Christina J. Carter, J. Mark Requena, Jesús R. PLoS Pathog Research Article 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. Public Library of Science 2012-03-01 /pmc/articles/PMC3291653/ /pubmed/22396643 http://dx.doi.org/10.1371/journal.ppat.1002547 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Sajnani, Gustavo Silva, Christopher J. Ramos, Adriana Pastrana, Miguel A. Onisko, Bruce C. Erickson, Melissa L. Antaki, Elizabeth M. Dynin, Irina Vázquez-Fernández, Ester Sigurdson, Christina J. Carter, J. Mark Requena, Jesús R. PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc) |
title | PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc)
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title_full | PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc)
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title_fullStr | PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc)
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title_full_unstemmed | PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc)
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title_short | PK-sensitive PrP(Sc) Is Infectious and Shares Basic Structural Features with PK-resistant PrP(Sc)
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title_sort | pk-sensitive prp(sc) is infectious and shares basic structural features with pk-resistant prp(sc) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291653/ https://www.ncbi.nlm.nih.gov/pubmed/22396643 http://dx.doi.org/10.1371/journal.ppat.1002547 |
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