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首页> 外文期刊>Biochemistry >Effect of copper and manganese on the de novo generation of protease-resistant prion protein in yeast cells
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Effect of copper and manganese on the de novo generation of protease-resistant prion protein in yeast cells

机译：铜和锰对酵母细胞抗蛋白抗朊病毒蛋白的影响

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摘要

The prion protein (PrP) is the key protein implicated in diseases known as transmissible spongiform encephalopathies. PrP has been shown to bind manganese and copper, the latter being involved in the normal function of the protein. Indeed, upon expression in yeast we noted a major increase in intracellular copper and a decrease in manganese. Interestingly, protease-resistant PrPSc-like protein (PrPres) 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 copper chelators bathocuproinedisulfonic acid or clioquinol. Conclusively, PrP itself influences manganese and copper metabolism, and a replacement of copper in PrP complexes with manganese is highly likely under the 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 ion homeostasis and uncovers copper and, more severely, manganese ions as in vivo risk factors for the conversion into PrPSc.
机译：朊病毒蛋白（PRP）是关键蛋白质，其涉及称为传染性海绵状脑病的疾病。 PRP已被证明是结合锰和铜，后者参与蛋白质的正常功能。实际上，在酵母中表达后，我们注意到细胞内铜的主要增加和锰的减少。有趣的是，当在铜和/或锰补充培养基中生长PrP表达酵母细胞时，诱导蛋白酶抗性PRPSC样蛋白（PRPRES）形成。 SDS-PAGE中的PRP系形模式由锰占主导地位。这种构象过渡对EDTA治疗稳定，但不存在于铜螯合剂浴ChelopuproOn0磺酸或Clioquinol的存在下。结论，PRP本身影响锰和铜代谢，并且在铜耗尽的条件下，锰中PrP络合物中的铜替代铜或存在过量的铜和锰。我们的目前的研究表明，PRP参与在细胞内金属离子稳态和覆盖铜，更严重的锰离子，如体内危险因素转化为PRPSC。

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