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首页> 外文期刊>Biochemistry >Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins.
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Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins.

机译:二聚体到甜甜圈:2-半胱氨酸过氧化物酶的氧化还原敏感寡聚。

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摘要

2-Cys peroxiredoxins (Prxs) are a large and diverse family of peroxidases which, in addition to their antioxidant functions, regulate cell signaling pathways, apoptosis, and differentiation. These enzymes are obligate homodimers (alpha(2)), utilizing a unique intermolecular redox-active disulfide center for the reduction of peroxides, and are known to form two oligomeric states: individual alpha(2) dimers or doughnut-shaped (alpha(2))(5) decamers. Here we characterize both the oligomerization properties and crystal structure of a bacterial 2-Cys Prx, Salmonella typhimurium AhpC. Analytical ultracentrifugation and dynamic light scattering show that AhpC's oligomeric state is redox linked, with oxidization favoring the dimeric state. The 2.5 A resolution crystal structure (R = 18.5%, R(free) = 23.9%) of oxidized, decameric AhpC reveals a metastable oligomerization intermediate, allowing us to identify a loop that adopts distinct conformations associated with decameric and dimeric states, with disulfide bond formation favoring the latter. This molecular switch contains the peroxidatic cysteine and acts to buttress the oligomerization interface in the reduced, decameric enzyme. A structurally detailed catalytic cycle incorporating these ideas and linking activity to oligomeric state is presented. Finally, on the basis of sequence comparisons, we suggest that the enzymatic and signaling activities of all 2-Cys Prxs are regulated by a redox-sensitive dimer to decamer transition.
机译:2-Cys过氧化物酶(Prxs)是一个庞大而多样的过氧化物酶家族,除其抗氧化功能外,还调节细胞信号传导途径,细胞凋亡和分化。这些酶是专性的同型二聚体(alpha(2)),利用独特的分子间氧化还原活性二硫化物中心来减少过氧化物,并且已知会形成两种低聚状态:单独的alpha(2)二聚体或甜甜圈状(alpha(2 ))(5)骗子。在这里,我们表征细菌2-Cys Prx,鼠伤寒沙门氏菌AhpC的低聚特性和晶体结构。分析超速离心和动态光散射表明,AhpC的低聚状态是氧化还原连接的,氧化作用有利于二聚状态。氧化的十聚体AhpC的2.5 A分辨率晶体结构(R = 18.5%,R(游离)= 23.9%)揭示了亚稳的低聚中间体,使我们能够鉴定出一个环,该环采用与二聚体和十聚体和二聚体状态相关的独特构象有利于后者的键形成。该分子开关包含过氧化物半胱氨酸,并起到支持还原的十聚酶中的寡聚界面的作用。提出了结构上详细的催化循环,这些循环结合了这些思想并将活性与低聚物状态联系起来。最后,在序列比较的基础上,我们建议所有2-Cys Prxs的酶促和信号传导活性受氧化还原敏感的二聚体到decamer过渡的调控。

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