The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement
The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement
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DOI：
10.1038/nchembio.1071
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发表时间：
2012-11-01
影响因子：
14.8
通讯作者：
Hagen, Wilfred R.
中科院分区：
文献类型：
--
作者：
Ebrahimi, Kourosh Honarmand;Bill, Eckhard;Hagen, Wilfred R.
一个保守的铁结合位点，铁氧化酶中心，调节铁代谢中普遍存在的蛋白质铁蛋白的重要铁储存作用。通常认为两个Fe（II）同时结合铁氧化酶中心，并且氧化的Fe（III）-O（H）-Fe（III）产物自发地作为一个单元进入铁蛋白的空腔。相反，在一些细菌铁蛋白和古细菌铁蛋白中，在该中心的持久二铁辅基被认为介导核心形成的催化。使用结合实验和同位素标记的Fe-57（II）的组合，我们研究了两个系统的比较：铁蛋白从超嗜热古细菌厌氧菌激烈火球菌（PfFtn）和真核人类H铁蛋白（HuHF）。结果不支持两个范式模型中的任何一个;相反，它们提出了一个统一的机制，其中Fe（III）-O-Fe（III）单元驻留在铁氧化酶中心，直到它被Fe（II）顺序取代。
A conserved iron-binding site, the ferroxidase center, regulates the vital iron storage role of the ubiquitous protein ferritin in iron metabolism. It is commonly thought that two Fe(II) simultaneously bind the ferroxidase center and that the oxidized Fe(III)-O(H)-Fe(III) product spontaneously enters the cavity of ferritin as a unit. In contrast, in some bacterioferritins and in archaeal ferritins a persistent di-iron prosthetic group in this center is believed to mediate catalysis of core formation. Using a combination of binding experiments and isotopically labeled Fe-57(II), we studied two systems in comparison: the ferritin from the hyperthermophilic archaeal anaerobe Pyrococcus furiosus (PfFtn) and the eukaryotic human H ferritin (HuHF). The results do not support either of the two paradigmatic models; instead they suggest a unifying mechanism in which the Fe(III)-O-Fe(III) unit resides in the ferroxidase center until it is sequentially displaced by Fe(II).