Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1
Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1
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硫氧还蛋白 1 对普遍保守的 ATP 酶 YchF 的氧化还原激活
DOI：
10.1089/ars.2015.6272
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发表时间：
2016-01-20
影响因子：
6.6
通讯作者：
Koch, Hans-Georg
中科院分区：
文献类型：
--
作者：
Hannemann, Liya;Suppanz, Ida;Koch, Hans-Georg
目的：YchF/Ola 1是普遍保守的GTP酶家族的非传统成员，因为它们优先水解ATP而不是GTP。这些ATP酶与各种细胞过程和病理学有关，包括DNA修复、肿瘤发生和凋亡。特别是，一个可能的作用，在调节氧化应激反应已被建议为细菌和人类YchF/Ola 1。在这项研究中，我们分析了YchF如何响应氧化应激，以及它如何潜在地调节抗氧化反应。结果：我们的数据确定氧化还原调节的单体-二聚体平衡的YchF的功能周期中的一个关键事件。在氧化应激时，保守的和表面暴露的半胱氨酸残基的氧化促进YchF二聚化，这伴随着ATP酶活性的抑制。在缺乏这种半胱氨酸的YchF突变体中没有观察到二聚体。在体外，YchF二聚体被硫氧还蛋白1（TrxA）解离，这刺激ATP酶活性。通过体内交联证明了YchF-硫氧还蛋白1相互作用的生理意义，这在活细胞中验证了这种相互作用。该方法还揭示了YchF的ATP酶结构域和螺旋结构域都与TrxA接触。创新：YchF/Ola 1是普遍保守的GTdR家族的第一个氧化还原调节成员，并且通过核苷酸结合基序内的保守半胱氨酸残基的氧化而失活。结论：我们的数据提供了新的见解到目前为止不明确的YchF/Ola 1蛋白质家族的调节，并规定其作为氧化应激反应的负调节剂的作用。抗氧化剂。氧化还原信号。24，141-156.
Aims: YchF/Ola1 are unconventional members of the universally conserved GTPase family because they preferentially hydrolyze ATP rather than GTP. These ATPases have been associated with various cellular processes and pathologies, including DNA repair, tumorigenesis, and apoptosis. In particular, a possible role in regulating the oxidative stress response has been suggested for both bacterial and human YchF/Ola1. In this study, we analyzed how YchF responds to oxidative stress and how it potentially regulates the antioxidant response. Results: Our data identify a redox-regulated monomer-dimer equilibrium of YchF as a key event in the functional cycle of YchF. Upon oxidative stress, the oxidation of a conserved and surface-exposed cysteine residue promotes YchF dimerization, which is accompanied by inhibition of the ATPase activity. No dimers were observed in a YchF mutant lacking this cysteine. In vitro, the YchF dimer is dissociated by thioredoxin 1 (TrxA) and this stimulates the ATPase activity. The physiological significance of the YchF-thioredoxin 1 interaction was demonstrated by in vivo cross-linking, which validated this interaction in living cells. This approach also revealed that both the ATPase domain and the helical domain of YchF are in contact with TrxA. Innovation: YchF/Ola1 are the first redox-regulated members of the universally conserved GTPase family and are inactivated by oxidation of a conserved cysteine residue within the nucleotide-binding motif. Conclusion: Our data provide novel insights into the regulation of the so far ill-defined YchF/Ola1 family of proteins and stipulate their role as negative regulators of the oxidative stress response. Antioxid. Redox Signal. 24, 141-156.