Alcohol oxidase (AOX1) from Pichia pastoris is a novel inhibitor of prion propagation and a potential ATPase
Alcohol oxidase (AOX1) from Pichia pastoris is a novel inhibitor of prion propagation and a potential ATPase
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DOI：
10.1111/j.1365-2958.2008.06557.x
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发表时间：
2009-02
影响因子：
3.6
通讯作者：
Hong Zhang;H. Loovers;Li-qiong Xu;Mingzhu Wang;P. Rowling;L. Itzhaki;W. Gong;Jun‐mei Zhou;G. Jon
中科院分区：
文献类型：
--
作者：
Hong Zhang;H. Loovers;Li-qiong Xu;Mingzhu Wang;P. Rowling;L. Itzhaki;W. Gong;Jun‐mei Zhou;G. Jon
先前的结果表明，甲基营养酵母可能含有调节朊病毒稳定性的因子。酒精氧化酶 (AOX) 是甲醇代谢中的关键酶，是甲基营养酵母特有的丰富蛋白质。我们研究了毕赤酵母 AOX1 对酿酒酵母朊病毒表型的影响。酿酒酵母朊病毒状态[PSI+]和[URE3]分别由蛋白质Sup35p和Ure2p的聚集产生，并且与Sup35p和Ure2p在体外形成淀粉样蛋白样原纤维的能力相关。我们发现酿酒酵母中巴斯德毕赤酵母AOX1的表达对[PSI+]朊病毒的增殖没有影响，但抑制[URE3]的增殖。在原纤维形成过程的早期添加 AOX1 可抑制体外 Ure2p 原纤维形成。 AOX1 以前未被鉴定为 ATP 酶。然而，我们发现除了黄素腺嘌呤二核苷酸依赖性 AOX 活性外，AOX1 还具有 ATP 酶活性。这项研究将 AOX1 确定为一种新型朊病毒抑制因子和潜在的 ATP 酶。
Previous results suggest that methylotrophic yeasts may contain factors that modulate prion stability. Alcohol oxidase (AOX), a key enzyme in methanol metabolism, is an abundant protein that is specific to methylotrophic yeasts. We examined the effect of Pichia pastoris AOX1 on prion phenotypes in Saccharomyces cerevisiae. The S. cerevisiae prion states [PSI+] and [URE3] arise from aggregation of the proteins Sup35p and Ure2p respectively, and correlate with the ability of Sup35p and Ure2p to form amyloid‐like fibrils in vitro. We found that expression of P. pastoris AOX1 in S. cerevisiae had no effect on propagation of the [PSI+] prion, but inhibited propagation of [URE3]. Addition of AOX1 early in the time‐course of fibril formation inhibits Ure2p fibril formation in vitro. AOX1 has not previously been identified as an ATPase. However, we discovered that in addition to its flavin adenine dinucleotide‐dependent AOX activity, AOX1 possesses ATPase activity. This study identifies AOX1 as a novel prion inhibitory factor and a potential ATPase.