The HBx protein from hepatitis B virus coordinates a redox-active Fe-S cluster.
The HBx protein from hepatitis B virus coordinates a redox-active Fe-S cluster.
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DOI：
10.1016/j.jbc.2022.101698
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发表时间：
2022-04
影响因子：
4.8
通讯作者：
Pandelia, Maria-Eirini
中科院分区：
文献类型：
--
作者：
Ueda, Chie;Langton, Michelle;Chen, Jiahua;Pandelia, Maria-Eirini
病毒蛋白HBx是B型肝炎病毒（HBV）的关键调节因子，并且是HBV相关肝病（例如肝硬化和肝细胞癌）的主要病因。从历史上看，HBx一直无视生物化学和结构表征，阻碍了理解其分子机制的努力。在这里，我们表明，可溶性HBx融合的可溶性标签copurifies与[2Fe-2S]或[4Fe-4S]集群，一个功能，是共享的五个HBV基因型。我们发现，O2稳定的[2Fe-2S]簇形式转化为O2敏感的[4Fe-4S]状态时，与化学还原剂反应，最好的描述是由还原偶联机制，让人想起Fe-S簇支架蛋白的转换。此外，Fe-S团簇的转化在连续的还原-氧化循环中是部分可逆的，团簇的损失主要发生在（再）氧化过程中。[4Fe-4S]2+/1+电对的负还原电位（−520 mV）表明，电池中不可能发生电子转移。总的来说，我们的研究结果确定HBx作为Fe-S蛋白与Fe-S支架蛋白在簇类型和还原转化方面具有惊人的相似性。HBx中的Fe-S簇为其以前未知的分子特性提供了新的见解，并为破译HBx相关铁（错误）调节和活性氧在肝脏肿瘤发生中的作用奠定了基础。
The viral protein HBx is the key regulatory factor of the hepatitis B virus (HBV) and the main etiology for HBV-associated liver diseases, such as cirrhosis and hepatocellular carcinoma. Historically, HBx has defied biochemical and structural characterization, deterring efforts to understand its molecular mechanisms. Here we show that soluble HBx fused to solubility tags copurifies with either a [2Fe-2S] or a [4Fe-4S] cluster, a feature that is shared among five HBV genotypes. We show that the O2-stable [2Fe-2S] cluster form converts to an O2-sensitive [4Fe-4S] state when reacted with chemical reductants, a transformation that is best described by a reductive coupling mechanism reminiscent of Fe-S cluster scaffold proteins. In addition, the Fe-S cluster conversions are partially reversible in successive reduction–oxidation cycles, with cluster loss mainly occurring during (re)oxidation. The considerably negative reduction potential of the [4Fe-4S]2+/1+ couple (−520 mV) suggests that electron transfer may not be likely in the cell. Collectively, our findings identify HBx as an Fe-S protein with striking similarities to Fe-S scaffold proteins both in cluster type and reductive transformation. An Fe-S cluster in HBx offers new insights into its previously unknown molecular properties and sets the stage for deciphering the roles of HBx-associated iron (mis)regulation and reactive oxygen species in the context of liver tumorigenesis.
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影响因子：
16.6
作者：
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