Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Biol Chem. 2012 Sep 7;287(37):31406-13. doi: 10.1074/jbc.M112.352617. Epub 2012 Jul 9.
The Escherichia coli protein IscU serves as the scaffold for Fe-S cluster assembly and the vehicle for Fe-S cluster transfer to acceptor proteins, such as apoferredoxin. IscU populates two conformational states in solution, a structured conformation (S) that resembles the conformation of the holoprotein IscU-[2Fe-2S] and a dynamically disordered conformation (D) that does not bind metal ions. NMR spectroscopic results presented here show that the specialized Hsp70 chaperone (HscA), alone or as the HscA-ADP complex, preferentially binds to and stabilizes the D-state of IscU. IscU is released when HscA binds ATP. By contrast, the J-protein HscB binds preferentially to the S-state of IscU. Consistent with these findings, we propose a mechanism in which cluster transfer is coupled to hydrolysis of ATP bound to HscA, conversion of IscU to the D-state, and release of HscB.
大肠杆菌蛋白 IscU 可作为 Fe-S 簇组装的支架，也是 Fe-S 簇向 apoferredoxin 等受体蛋白转移的载体。IscU 在溶液中存在两种构象状态，一种是结构构象（S），类似于全蛋白 IscU-[2Fe-2S]的构象，另一种是动态无序构象（D），不结合金属离子。本文介绍的 NMR 光谱结果表明，专门的 Hsp70 伴侣蛋白（HscA），无论是单独存在还是作为 HscA-ADP 复合物，都优先结合并稳定 IscU 的 D 态。当 HscA 结合 ATP 时，IscU 被释放。相比之下，J 蛋白 HscB 优先结合 IscU 的 S 态。与这些发现一致，我们提出了一种机制，其中簇转移与结合在 HscA 上的 ATP 水解、IscU 转化为 D 态以及 HscB 的释放相偶联。
