Department of Chemistry and Center for Photochemical Sciences , Bowling Green State University , Bowling Green , Ohio 43403 , United States.
ACS Chem Biol. 2018 Mar 16;13(3):591-599. doi: 10.1021/acschembio.7b00442. Epub 2018 Jan 3.
IscU, the central scaffold protein in the bacterial ISC iron-sulfur (Fe-S) cluster biosynthesis system, has long been recognized to bind a Zn ion at its active site. While initially regarded as an artifact, Zn binding has been shown to induce stabilization of the IscU structure that may mimic a state biologically relevant to IscU's role in Fe-S cluster biosynthesis. More recent studies have revealed that SufU, a homologous protein involved in Fe-S cluster biosynthesis in Gram-positive bacteria, also binds a Zn ion with structural implications. Given the widespread occurrence of the "IscU-like" protein fold, particularly among Fe-S cluster biosynthesis systems, an interesting question arises as to whether Zn ion binding and the resulting structural alterations are common properties in IscU-like proteins. Interactions between IscU and specific metal ions are investigated and compared side-by-side with those of SufU from a representative Gram-positive bacterium in the phylum Firmicutes. These studies were extended with additional transition metal ions chosen to investigate the influence of coordination geometry on selectivity for binding at the active sites of IscU and SufU. Monitoring and comparing the conformational behavior and stabilization afforded by different transition metal ions upon IscU and SufU revealed similarities between the two proteins and suggest that metal-dependent conformational transitions may be characteristic of U-type proteins involved in Fe-S cluster biosynthesis.
ISC 中的中央支架蛋白 IscU 长期以来一直被认为在其活性部位结合一个 Zn 离子。虽然最初被认为是一种假象，但 Zn 结合已被证明可以诱导 IscU 结构的稳定，这种稳定可能模拟了 IscU 在 Fe-S 簇生物合成中的生物学相关状态。最近的研究表明，SufU，一种参与革兰氏阳性菌 Fe-S 簇生物合成的同源蛋白，也结合了一个具有结构意义的 Zn 离子。鉴于“ISCU 样”蛋白折叠的广泛存在，特别是在 Fe-S 簇生物合成系统中，一个有趣的问题出现了，即 Zn 离子结合和由此产生的结构改变是否是 IscU 样蛋白的共同特性。研究了 IscU 与特定金属离子的相互作用，并与来自厚壁菌门的代表性革兰氏阳性菌 SufU 的相互作用进行了并列比较。这些研究通过选择额外的过渡金属离子进行了扩展，以研究配位几何结构对 IscU 和 SufU 活性部位结合选择性的影响。监测和比较不同过渡金属离子对 IscU 和 SufU 构象行为和稳定性的影响，揭示了这两种蛋白质之间的相似性，并表明金属依赖性构象转变可能是参与 Fe-S 簇生物合成的 U 型蛋白的特征。
