Molecular organization, biochemical function, cellular role and evolution of NfuA, an atypical Fe-S carrier
Molecular organization, biochemical function, cellular role and evolution of NfuA, an atypical Fe-S carrier
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DOI：
10.1111/j.1365-2958.2012.08181.x
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Barras, Frederic
中科院分区：
文献类型：
--
作者：
Py, Beatrice;Gerez, Catherine;Barras, Frederic
铁硫 (Fe-S) 蛋白质的生物合成由多蛋白质系统 ISC 和 SUF 催化。然而，在原核生物和真核生物中均已描述了非 ISC、非 SUF Fe-S 生物合成因子。在这里，我们报告了这种非 ISC、非 SUF 成分 Nfu 蛋白的体外和体内研究。系统基因组分析使我们能够定义四个亚科。大肠杆菌 NfuA 属于 II 亚科。该亚家族的大多数成员都具有与缺乏 Fe-S 簇协调 Cys 配体的简并 A 型载体结构域 (ATC*) 融合的 Nfu 结构域。 Nfu 结构域结合 [4Fe-4S] 簇，而 ATC* 结构域与 NuoG（复合物 I 亚基）和乌头酸酶 B (AcnB) 相互作用。在体外，holo-NfuA 促进 AcnB 的成熟。在体内，NfuA 对于复合物 I 在有氧生长条件下以及 AcnB 在超氧化物存在下的完全活性是必需的。 NfuA 从 IscU/HscBA 和 SufBCD 支架接收 Fe-S 簇，并最终将它们转移到 ATC IscA 和 SufA。这项研究提供了有关 Fe-S 生物发生因子之一的重要信息，该因子经常被 ISC 和/或 SUF 合成生物体（包括细菌、植物和动物）用作构建块。
Biosynthesis of ironsulphur (Fe-S) proteins is catalysed by multi-protein systems, ISC and SUF. However, non-ISC, non-SUF Fe-S biosynthesis factors have been described, both in prokaryotes and eukaryotes. Here we report in vitro and in vivo investigations of such a non-ISC, non SUF component, the Nfu proteins. Phylogenomic analysis allowed us to define four subfamilies. Escherichia coli NfuA is within subfamily II. Most members of this subfamily have a Nfu domain fused to a degenerate A-type carrier domain (ATC*) lacking Fe-S cluster co-ordinating Cys ligands. The Nfu domain binds a [4Fe-4S] cluster while the ATC* domain interacts with NuoG (a complex I subunit) and aconitase B (AcnB). In vitro, holo-NfuA promotes maturation of AcnB. In vivo, NfuA is necessary for full activity of complex I under aerobic growth conditions, and of AcnB in the presence of superoxide. NfuA receives Fe-S clusters from IscU/HscBA and SufBCD scaffolds and eventually transfers them to the ATCs IscA and SufA. This study provides significant information on one of the Fe-S biogenesis factors that has been often used as a building block by ISC and/or SUF synthesizing organisms, including bacteria, plants and animals.