A novel group of glutaredoxins in the cis-Golgi critical for oxidative stress resistance
A novel group of glutaredoxins in the cis-Golgi critical for oxidative stress resistance
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DOI：
10.1091/mbc.e07-09-0896
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Herrmann, Johannes M.
中科院分区：
文献类型：
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作者：
Mesecke, Nikola;Spang, Anne;Herrmann, Johannes M.
谷氧还蛋白是一个普遍存在的蛋白质家族，通过使用还原型谷胱甘肽催化其底物蛋白中二硫键的还原。为了鉴定面包酵母中谷氧还蛋白的完整组成，我们发现了三种迄今为止尚未表征的谷氧还蛋白样蛋白，我们将其命名为Grx 6、Grx 7和Grx 8。Grx 6和Grx 7代表与N-末端信号序列合成的密切相关的单硫醇谷氧还蛋白。这两种蛋白质都位于顺式高尔基体中，从而代表了在分泌途径的隔室中发现的第一种谷氧还蛋白。与先前描述的单硫醇谷氧还蛋白相反，Grx 6和Grx 7在体外显示出高的谷氧还蛋白活性。Grx 6和Grx 7在它们的活性上重叠，缺乏这两种蛋白质的缺失突变体显示出生长缺陷和对氧化剂如过氧化氢或二酰胺的强烈增加的敏感性。我们的观察结果表明，Grx 6和Grx 7不发挥一般的作用，在早期分泌途径中的蛋白质的氧化折叠，而是抵消特定的巯基在底物蛋白的氧化。
Glutaredoxins represent a ubiquitous family of proteins that catalyze the reduction of disulfide bonds in their substrate proteins by use of reduced glutathione. In an attempt to identify the full complement of glutaredoxins in baker's yeast, we found three so-far uncharacterized glutaredoxin-like proteins that we named Grx6, Grx7, and Grx8. Grx6 and Grx7 represent closely related monothiol glutaredoxins that are synthesized with N-terminal signal sequences. Both proteins are located in the cis-Golgi, thereby representing the first glutaredoxins found in a compartment of the secretory pathway. In contrast to formerly described monothiol glutaredoxins, Grx6 and Grx7, showed a high glutaredoxin activity in vitro. Grx6 and Grx7 overlap in their activity and deletion mutants lacking both proteins show growth defects and a strongly increased sensitivity toward oxidizing agents such as hydrogen peroxide or diamide. Our observations suggest that Grx6 and Grx7 do not play a general role in the oxidative folding of proteins in the early secretory pathway but rather counteract the oxidation of specific thiol groups in substrate proteins.