Effect of Copper and Manganese on the de Novo Generation of Protease-Resistant Prion Protein in Yeast Cells

详细信息    查看全文

• 作者：Carina Treiber ; Andreas Simons ; and Gerd Multhaup
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：May 30, 2006
• 年：2006
• 卷：45
• 期：21
• 页码：6674 - 6680
• 全文大小：301K
• 年卷期：v.45,no.21(May 30, 2006)
• ISSN：1520-4995

文摘

The prion protein (PrP) is the key protein implicated in diseases known as transmissiblespongiform encephalopathies. PrP has been shown to bind manganese and copper, the latter being involvedin the normal function of the protein. Indeed, upon expression in yeast we noted a major increase inintracellular copper and a decrease in manganese. Interestingly, protease-resistant PrP^Sc-like protein (PrP^res)formation was induced when PrP-expressing yeast cells were grown in copper- and/or manganese-supplemented media. The pattern of PrP banding in SDS-PAGE was dominantly determined by manganese.This conformational transition was stable against EDTA treatment but not in the presence of the copperchelators bathocuproinedisulfonic acid or clioquinol. Conclusively, PrP itself influences manganese andcopper metabolism, and a replacement of copper in PrP complexes with manganese is highly likely underthe condition of copper depletion or if excess amounts of copper and manganese are present. Taken together,our present study demonstrates the involvement of PrP in the regulation of intracellular metal ionhomeostasis and uncovers copper and, more severely, manganese ions as in vivo risk factors for theconversion into PrP^Sc.