Mutational analysis of Sse1 (Hsp110) suggests an integral role for this chaperone in yeast prion propagation in vivo.
Mutational analysis of Sse1 (Hsp110) suggests an integral role for this chaperone in yeast prion propagation in vivo.
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Sse1 (Hsp110) 的突变分析表明该伴侣在酵母朊病毒体内传播中发挥着不可或缺的作用
DOI：
10.1534/g3.113.007112
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发表时间：
2013-08-07
期刊：
影响因子：
--
通讯作者：
Jones GW
中科院分区：
文献类型：
--
作者：
Moran C;Kinsella GK;Zhang ZR;Perrett S;Jones GW
酵母Hsp110分子伴侣Sse 1是一个保守的蛋白质，是Hsp70蛋白超家族的非经典成员。Sse1影响细胞对热应激的反应，并且还被认为在酵母中朊病毒的繁殖中发挥作用。Sse 1似乎可以通过直接或间接影响典型胞质Hsp70的核苷酸交换活性来发挥其在体内的作用。使用遗传筛选的基础上无法繁殖的酵母[PSI+]朊病毒，我们已经确定了13个新的Sse1突变体，预计通过各种不同的机制改变伴侣蛋白的功能。这些新的Sse 1突变体不仅在繁殖和治愈酵母朊病毒的能力上发生了改变，而且在高温下生长的能力也发生了不同程度的改变。已知影响酵母朊病毒繁殖的伴侣蛋白的表达水平在Sse1突变体中没有改变，这表明所观察到的表型效应是由这些突变体中的直接功能改变引起的。将突变体的位置映射到Sse1晶体结构上表明，Sse1中不止一个功能改变可能导致朊病毒繁殖和在高温下发挥作用的能力发生变化。所有分离的Sse 1突变体在正常生长条件下在细胞中提供必需的功能，进一步证明体内必需的伴侣蛋白功能至少可以在某种程度上与朊病毒繁殖相关的功能分离。我们的研究结果表明，Sse1可以通过各种不同的机制影响朊病毒的传播。
The yeast Hsp110 chaperone Sse1 is a conserved protein that is a noncanonical member of the Hsp70 protein superfamily. Sse1 influences the cellular response to heat stress and has also been implicated in playing a role in the propagation of prions in yeast. Sse1 can seemingly exert its effects in vivo through direct or indirect actions by influencing the nucleotide exchange activity of canonical cytosolic Hsp70s. Using a genetic screen based on the inability to propagate the yeast [PSI+] prion, we have identified 13 new Sse1 mutants that are predicted to alter chaperone function through a variety of different mechanisms. Not only are these new Sse1 mutants altered in the ability to propagate and cure yeast prions but also to varying degrees in the ability to grow at elevated temperatures. The expression levels of chaperone proteins known to influence yeast prion propagation are unaltered in the Sse1 mutants, suggesting that the observed phenotypic effects are caused by direct functional alterations in these mutants. Mapping the location of the mutants onto the Sse1 crystal structure suggests that more than one functional alteration in Sse1 may result in changes in prion propagation and ability to function at elevated temperatures. All Sse1 mutants isolated provide essential functions in the cell under normal growth conditions, further demonstrating that essential chaperone functions in vivo can to some degree at least be detached from those related to propagation of prions. Our results suggest that Sse1 can influence prion propagation through a variety of different mechanisms.
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