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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #353088
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies

Location: Virus and Prion Research

Title: Divalent cation effects on elk prion protein stability and fibril formation

Author
item Nicholson, Eric
item SAMORODNITSKY, DANIEL - Orise Fellow

Submitted to: Prion
Publication Type: Abstract Only
Publication Acceptance Date: 4/22/2018
Publication Date: 5/22/2018
Citation: Nicholson, E.M., Samorodnitsky, D. 2018. Divalent cation effects on elk prion protein stability and fibril formation. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Poster No. P14, p. 53.

Interpretive Summary:

Technical Abstract: Misfolding of the normally folded prion protein of mammals (PrPC) into infectious fibrils causes a variety of diseases, including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE) in cattle. The misfolded form of PrPC, termed PrPSc, or in the case of CWD, 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 divalent cations as well. The significance of this binding 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 (M132 and L132) in the mature form of the prion protein (amino acids 26-234). We find that copper and zinc both de-stabilize 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 more susceptible. However, in vitro conversion of PrP is suppressed equally by either copper or zinc, in both L132 and M132 PrP. This report demonstrates the complex importance of ionic character on the PrPC folding pathway selection on the route to PrPSc formation.