Redox-regulated chaperones.-猫眼课题宝

DOI：

10.1021/bi9003556

发表时间：

2009-06-09

期刊：

BIOCHEMISTRY

影响因子：

2.9

通讯作者：

中科院分区：

生物学3区

文献类型：

作者：

Kumsta, Caroline;Jakob, Ursula

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848813/?report=classic

应激蛋白（如分子伴侣）的氧化还原调节保证了对氧化应激条件的立即响应。本文综述了两类主要的氧化还原调节分子伴侣，细菌中的Hsp 33和真核生物中典型的2-Cys过氧化物酶。这两种蛋白质都采用氧化还原敏感的半胱氨酸，其氧化状态直接控制它们对展开蛋白质的亲和力，因此控制它们的伴侣功能。我们将首先讨论热休克蛋白33，其氧化应激诱导的二硫键形成触发分子伴侣的部分解折叠，这反过来又导致未折叠蛋白质的高亲和力结合位点的暴露。这种快速活化模式使得Hsp 33对于保护细菌免受严重氧化应激条件如次氯酸盐（即，漂白）处理，这导致广泛的蛋白质解折叠和聚集。我们将比较热休克蛋白33的高度丰富的真核生物典型的2-半胱氨酸过氧化物酶，其氧化应激诱导的亚磺酸形成变成一个分子伴侣过氧化物酶在体外，大概在体内。这些例子说明了蛋白质如何使用可逆的半胱氨酸修饰来快速适应氧化应激条件，并证明氧化还原调节在保护生物体免受活性氧介导的细胞死亡中起着至关重要的作用。

Redox regulation of stress proteins, such as molecular chaperones, guarantees an immediate response to oxidative stress conditions. This review focuses on the two major classes of redox-regulated chaperones, Hsp33 in bacteria and typical 2-Cys peroxiredoxins in eukaryotes. Both proteins employ redox-sensitive cysteines, whose oxidation status directly controls their affinity for unfolding proteins and therefore their chaperone function. We will first discuss Hsp33, whose oxidative stress-induced disulfide bond formation triggers the partial unfolding of the chaperone, which, in turn, leads to the exposure of a high-affinity binding site for unfolded proteins. This rapid mode of activation makes Hsp33 essential for protecting bacteria against severe oxidative stress conditions, such as hypochlorite (i.e., bleach) treatment, which leads to widespread protein unfolding and aggregation. We will compare Hsp33 to the highly abundant eukaryotic typical 2-Cys peroxiredoxin, whose oxidative stress-induced sulfinic acid formation turns the peroxidase into a molecular chaperone in vitro and presumably in vivo. These examples illustrate how proteins use reversible cysteine modifications to rapidly adjust to oxidative stress conditions and demonstrate that redox regulation plays a vital role in protecting organisms against reactive oxygen species-mediated cell death.