Differential effects of divalent cations on elk prion protein fibril formation and stability
Abstract
Misfolding of the normally folded prion protein of mammals (PrPC) into infectious fibrils causes a variety of diseases, from scrapie in sheep to chronic wasting disease (CWD) in cervids. The misfolded form of PrPC, termed PrPSc, or in this case PrPCWD, interacts with PrPC to create more PrPCWD. This process is not clearly defined but is affected by the presence and interactions of biotic and abiotic cofactors. These include nucleic acids, lipids, glycosylation, pH, and ionic character. PrPC has been shown to act as a copper-binding protein in vivo, though it also binds to other divalents as well. The significance of this action has not been conclusively elucidated. Previous reports have shown that metal binding sites occur throughout the N-terminal region of PrPC. Other cations like manganese have also been shown to affect PrPC abundance in a transcript-independent fashion. Here, we examined the ability of different divalent cations to influence the stability and in vitro conversion of two variants of PrP from elk (L/M132, 26–234). We find that copper and zinc destabilize PrP. We also find that PrP M132 exhibits a greater degree of divalent cation induced destabilization than L132. This supports findings that leucine at position 132 confers resistancemore »
- Authors:
-
- Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States); United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, IA (United States)
- United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, IA (United States)
- Publication Date:
- Research Org.:
- Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1494691
- Grant/Contract Number:
- AC05-06OR23100
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Prion
- Additional Journal Information:
- Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 1933-6896
- Publisher:
- Taylor & Francis
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Prion; chronic wasting disease; PrP; transmissible spongiform encephalopathies; cervid; CWD; amyloid; misfolding
Citation Formats
Samorodnitsky, Daniel, and Nicholson, Eric M. Differential effects of divalent cations on elk prion protein fibril formation and stability. United States: N. p., 2018.
Web. doi:10.1080/19336896.2017.1423187.
Samorodnitsky, Daniel, & Nicholson, Eric M. Differential effects of divalent cations on elk prion protein fibril formation and stability. United States. doi:10.1080/19336896.2017.1423187.
Samorodnitsky, Daniel, and Nicholson, Eric M. Tue .
"Differential effects of divalent cations on elk prion protein fibril formation and stability". United States. doi:10.1080/19336896.2017.1423187. https://www.osti.gov/servlets/purl/1494691.
@article{osti_1494691,
title = {Differential effects of divalent cations on elk prion protein fibril formation and stability},
author = {Samorodnitsky, Daniel and Nicholson, Eric M.},
abstractNote = {Misfolding of the normally folded prion protein of mammals (PrPC) into infectious fibrils causes a variety of diseases, from scrapie in sheep to chronic wasting disease (CWD) in cervids. The misfolded form of PrPC, termed PrPSc, or in this case PrPCWD, interacts with PrPC to create more PrPCWD. This process is not clearly defined but is affected by the presence and interactions of biotic and abiotic cofactors. These include nucleic acids, lipids, glycosylation, pH, and ionic character. PrPC has been shown to act as a copper-binding protein in vivo, though it also binds to other divalents as well. The significance of this action has not been conclusively elucidated. Previous reports have shown that metal binding sites occur throughout the N-terminal region of PrPC. Other cations like manganese have also been shown to affect PrPC abundance in a transcript-independent fashion. Here, we examined the ability of different divalent cations to influence the stability and in vitro conversion of two variants of PrP from elk (L/M132, 26–234). We find that copper and zinc destabilize PrP. We also find that PrP M132 exhibits a greater degree of divalent cation induced destabilization than L132. This supports findings that leucine at position 132 confers resistance to CWD, while M132 is susceptible. However, in vitro conversion of PrP is equally suppressed by either copper or zinc, in both L132 and M132 backgrounds. This report demonstrates the complex importance of ionic character on the PrPC folding pathway selection on the route to PrPSc formation.},
doi = {10.1080/19336896.2017.1423187},
journal = {Prion},
number = 1,
volume = 12,
place = {United States},
year = {2018},
month = {1}
}
Web of Science
Figures / Tables:

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Figures / Tables found in this record: