Department of Biotechnology, Delft University of Technology, Delft, The Netherlands.
Nat Chem Biol. 2012 Nov;8(11):941-8. doi: 10.1038/nchembio.1071. Epub 2012 Sep 23.
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 (57)Fe(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).
一个保守的铁结合位点，即亚铁氧化酶中心，调节着普遍存在的蛋白铁蛋白在铁代谢中的重要铁储存作用。人们普遍认为，两个 Fe(II) 同时结合亚铁氧化酶中心，氧化的 Fe(III)-O(H)-Fe(III) 产物自发地作为一个单位进入铁蛋白的腔中。相比之下，在一些细菌铁蛋白和古菌铁蛋白中，人们认为该中心的持久双铁辅基介导了核心形成的催化作用。我们使用结合实验和同位素标记的 (57)Fe(II) 研究了两个系统：来自高温厌氧菌 Pyrococcus furiosus 的铁蛋白 (PfFtn) 和真核生物人 H 铁蛋白 (HuHF)。结果既不支持这两种典范模型中的任何一种；相反，它们提出了一个统一的机制，其中 Fe(III)-O-Fe(III) 单元位于亚铁氧化酶中心，直到它被 Fe(II) 顺序取代。
