Genetic and biochemical studies have led to the identification of several cellular pathways for the biosynthesis of iron-sulfur proteins in different organisms. The most broadly distributed and highly conserved system involves an Hsp70 chaperone and J-protein co-chaperone system that interacts with a scaffold-like protein involved in [FeS]-cluster preassembly. Specialized forms of Hsp70 and their co-chaperones have evolved in bacteria (HscA, HscB) and in certain fungi (Ssq1, Jac1), whereas most eukaryotes employ a multifunctional mitochondrial Hsp70 (mtHsp70) together with a specialized co-chaperone homologous to HscB/Jac1. HscA and Ssq1 have been shown to specifically bind to a conserved sequence present in the [FeS]-scaffold protein designated IscU in bacteria and Isu in fungi, and the crystal structure of a complex of a peptide containing the IscU recognition region bound to the HscA substrate binding domain has been determined. The interaction of IscU/Isu with HscA/Ssq1 is regulated by HscB/Jac1 which bind the scaffold protein to assist delivery to the chaperone and stabilize the chaperone-scaffold complex by enhancing chaperone ATPase activity. The crystal structure of HscB reveals that the N-terminal J-domain involved in regulation of HscA ATPase activity is similar to other J-proteins, whereas the C-terminal domain is unique and appears to mediate specific interactions with IscU. At the present time the exact function(s) of chaperone-[FeS]-scaffold interactions in iron-sulfur protein biosynthesis remain(s) to be established. In vivo and in vitro studies of yeast Ssq1 and Jac1 indicate that the chaperones are not required for [FeS]-cluster assembly on Isu. Recent in vitro studies using bacterial HscA, HscB and IscU have shown that the chaperones destabilize the IscU[FeS] complex and facilitate cluster delivery to an acceptor apo-protein consistent with a role in regulating cluster release and transfer. Additional genetic and biochemical studies are needed to extend these findings to mtHsp70 activities in higher eukaryotes.

中文翻译：

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分子伴侣HscA / Ssq1和HscB / Jac1及其在铁硫蛋白成熟中的作用。

遗传和生化研究已经确定了在不同生物中生物合成铁硫蛋白的几种细胞途径。最广泛分布和高度保守的系统涉及Hsp70分子伴侣和J蛋白共分子伴侣系统，该系统与参与[FeS]簇预组装的支架样蛋白相互作用。Hsp70及其副伴侣的特殊形式已经在细菌（HscA，HscB）和某些真菌（Ssq1，Jac1）中进化，而大多数真核生物均使用多功能线粒体Hsp70（mtHsp70）以及与HscB /杰克1。已显示HscA和Ssq1与细菌中称为IscU的[FeS]支架蛋白和真菌中的Isu的保守序列特异性结合，并且已经确定了包含与HscA底物结合域结合的IscU识别区的肽的复合物的晶体结构。IscU / Isu与HscA / Ssq1的相互作用受HscB / Jac1的调控，后者结合支架蛋白以协助递送至分子伴侣并通过增强分子伴侣ATPase活性来稳定分子伴侣-支架复合物。HscB的晶体结构表明，参与调节HscA ATPase活性的N末端J结构域与其他J蛋白相似，而C末端结构域是独特的并且似乎介导与IscU的特定相互作用。目前，在铁-硫蛋白生物合成中分子伴侣-[FeS]-支架相互作用的确切功能尚待确定。酵母Ssq1和Jac1的体内和体外研究表明，在Isu上[FeS]-簇组装不需要分子伴侣。最近使用细菌HscA，HscB和IscU进行的体外研究表明，伴侣分子破坏了IscU [FeS]复合物的稳定性，并促进了簇向受体载脂蛋白的传递，这与调节簇的释放和转移的作用一致。需要更多的遗传和生化研究，以将这些发现扩展到高等真核生物中的mtHsp70活性。