Sup35 methionine oxidation is a trigger for de novo [PSI(+)] prion formation.
Sup35 methionine oxidation is a trigger for de novo [PSI(+)] prion formation.
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DOI：
10.1080/19336896.2015.1065372
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发表时间：
2015
期刊：
影响因子：
2.3
通讯作者：
Grant CM
中科院分区：
文献类型：
--
作者：
Grant CM
摘要。真菌和哺乳动物朊病毒自发产生的分子基础知之甚少。已知许多不同的环境应激条件增加酵母[PSI+]朊病毒形成的频率，这与引起蛋白质错误折叠的条件可能促进正常可溶性蛋白质转化为它们的淀粉样蛋白形式的想法一致。我们实验室最近的一项研究表明，在缺乏关键抗氧化剂的酵母突变体中，[PSI+]朊病毒的从头形成显著增加，这表明内源性活性氧足以促进朊病毒的形成。我们的研究结果强烈暗示Sup35的氧化损伤是酵母中形成可遗传[PSI+]朊病毒的重要触发因素。本文综述了Sup35的直接氧化可能导致有利于转化为可传递的淀粉样蛋白形式的结构转变的机制。这类似于已经提出的触发哺乳动物朊病毒蛋白（PrPC）错误折叠成聚集的羊瘙痒病形式（PrPSc）的各种环境因素。
ABSTRACT. The molecular basis by which fungal and mammalian prions arise spontaneously is poorly understood. A number of different environmental stress conditions are known to increase the frequency of yeast [PSI+] prion formation in agreement with the idea that conditions which cause protein misfolding may promote the conversion of normally soluble proteins to their amyloid forms. A recent study from our laboratory has shown that the de novo formation of the [PSI+] prion is significantly increased in yeast mutants lacking key antioxidants suggesting that endogenous reactive oxygen species are sufficient to promote prion formation. Our findings strongly implicate oxidative damage of Sup35 as an important trigger for the formation of the heritable [PSI+] prion in yeast. This review discusses the mechanisms by which the direct oxidation of Sup35 might lead to structural transitions favoring conversion to the transmissible amyloid-like form. This is analogous to various environmental factors which have been proposed to trigger misfolding of the mammalian prion protein (PrPC) into the aggregated scrapie form (PrPSc).