Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA.
Int J Mol Sci. 2021 Jun 2;22(11):6006. doi: 10.3390/ijms22116006.
Iron-sulfur clusters are essential to almost every life form and utilized for their unique structural and redox-targeted activities within cells during many cellular pathways. Although there are three different Fe-S cluster assembly pathways in prokaryotes (the NIF, SUF and ISC pathways) and two in eukaryotes (CIA and ISC pathways), the iron-sulfur cluster (ISC) pathway serves as the central mechanism for providing 2Fe-2S clusters, directly and indirectly, throughout the entire cell in eukaryotes. Proteins central to the eukaryotic ISC cluster assembly complex include the cysteine desulfurase, a cysteine desulfurase accessory protein, the acyl carrier protein, the scaffold protein and frataxin (in humans, FS1, SD11, CP, SCU and XN, respectively). Recent molecular details of this complex (labeled from the first letter from each ISC protein outlined earlier), which exists as a dimeric pentamer, have provided real structural insight into how these partner proteins arrange themselves around the cysteine desulfurase, the core dimer of the () complex. In this review, we focus on both frataxin and the scaffold within the human, fly and yeast model systems to provide a better understanding of the biophysical characteristics of each protein alone and within the FXN/ISCU complex as it exists within the larger construct. These details support a complex dynamic interaction between the FXN and ISCU proteins when both are part of the complex and this provides additional insight into the coordinated mechanism of Fe-S cluster assembly.
铁硫簇对于几乎所有生命形式都是必不可少的，并且在细胞内的许多细胞途径中，利用其独特的结构和氧化还原靶向活性。尽管原核生物中有三种不同的铁硫簇组装途径（NIF、SUF 和 ISC 途径）和两种真核生物（CIA 和 ISC 途径），但铁硫簇（ISC）途径是为整个细胞提供 2Fe-2S 簇的核心机制，在真核生物中直接和间接地提供 2Fe-2S 簇。真核生物 ISC 簇组装复合物的核心蛋白包括半胱氨酸脱硫酶、半胱氨酸脱硫酶辅助蛋白、酰基载体蛋白、支架蛋白和铁蛋白（在人类中，分别为 FS1、SD11、CP、SCU 和 XN）。该复合物的最近分子细节（标记为前面概述的每个 ISC 蛋白的首字母），它作为二聚体五聚体存在，为这些伴侣蛋白如何围绕半胱氨酸脱硫酶、（）复合物的核心二聚体排列提供了真实的结构见解。在这篇综述中，我们重点关注人类、果蝇和酵母模型系统中的铁蛋白和支架，以更好地了解每个蛋白单独以及在 FXN/ISCU 复合物中的生物物理特性，因为它存在于更大的 结构中。这些细节支持 FXN 和 ISCU 蛋白在两者都是 复合物的一部分时之间复杂的动态相互作用，并为铁硫簇组装的协调机制提供了额外的见解。
