Moonlighting by different stressors: crystal structure of the chaperone species of a 2-Cys peroxiredoxin.

Moonlighting by different stressors: crystal structure of the chaperone species of a 2-Cys peroxiredoxin.
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DOI:
10.1016/j.str.2012.01.004
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发表时间:
2012-03-07
期刊:
影响因子:
5.7
通讯作者:
Angelucci, Francesco
Angelucci, Francesco
中科院分区:
生物学2区
文献类型:
--
作者:
Saccoccia, Fulvio;Di Micco, Patrizio;Boumis, Giovanna;Brunori, Maurizio;Koutris, Ilias;Miele, Adriana E.;Morea, Veronica;Sriratana, Palita;Williams, David L.;Bellelli, Andrea;Angelucci, Francesco

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2-半胱氨酸过氧化物酶(Prxs)根据细胞的生理状态发挥两种不同的作用。它们是低氧化应激下的硫氧还蛋白依赖性过氧化物酶,以及暴露于高过氧化物浓度时的ATP非依赖性伴侣。这些替代功能与低(LMW)至高(HMW)分子量物质的低聚状态变化相关。在这里,我们提出了曼氏血吸虫PrxI在两种状态下的结构:低分子量十聚体和高分子量20聚体,由两个堆叠的十聚体形成。后者是2-Cys Prx分子伴侣形式的第一个结构。结构的比较揭示了化学应激源,如高H2 O2浓度和酸性pH值,被感知并转化为该蛋白质家族中的功能开关的机制。我们还提出了一个模型来解释堆叠Prx环的长丝在体内的形成。
2-Cys peroxiredoxins (Prxs) play two different roles depending on the physiological status of the cell. They are thioredoxin-dependent peroxidases under low oxidative stress, and ATP-independent chaperones upon exposure to high peroxides concentrations. These alternative functions have been associated with changes in the oligomerization state from low (LMW) to high (HMW) molecular weight species. Here we present the structures of Schistosoma mansoni PrxI in both states: the LMW decamer and the HMW 20-mer, formed by two stacked decamers. The latter is the first structure of a 2-Cys Prx chaperonic form. Comparison of the structures sheds light on the mechanism by which chemical stressors, such as high H2O2 concentration and acidic pH, are sensed and translated into a functional switch in this protein family. We also propose a model to account for the in vivo formation of long filaments of stacked Prx rings.
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