The putative "nucleation site" in human H-chain ferritin is not required for mineralization of the iron core
The putative "nucleation site" in human H-chain ferritin is not required for mineralization of the iron core
复制标题
DOI：
10.1021/bi0498813
复制
发表时间：
2004-04-13
期刊：
影响因子：
2.9
通讯作者：
Chasteen, ND
中科院分区：
文献类型：
--
作者：
Bou-Abdallah, F;Biasiotto, G;Chasteen, ND
人们普遍认为，哺乳动物h链铁蛋白的假定成核位点（Glu61、Glu64和Glu67）在该蛋白的矿物核形成中起重要作用。对h链铁蛋白成核位点变异A2 （E61A/E64A/E67A）的研究传统上显示铁氧化活性和矿化受损。然而，最近的测量表明，先前观察到的损伤可能是由于蛋白质的铁氧化酶位点的破坏，因为Glu61是铁氧化酶和蛋白质成核位点的共享配体。本研究采用了一种新的成核位点变异A1 (E64A/E67A)，它保留了铁氧化酶位点配体Glu61。数据（O-2摄取，铁结合，常规和停止流动动力学测量）表明，变异a1保留了一个完全功能的氧化铁酶位点，具有与野生型人类h链蛋白相似的铁氧化和矿化特性。因此，与先前发表的文献相反，本研究表明，假定的“成核位点”在h链铁蛋白的铁摄取或矿化中并不起重要作用。
It is widely believed that the putative nucleation site (Glu61, Glu64, and Glu67) in mammalian H-chain ferritin plays an important role in mineral core formation in this protein. Studies of nucleation site variant A2 (E61A/E64A/E67A) of H-chain ferritin have traditionally shown impaired iron oxidation activity and mineralization. However, recent measurements have suggested that the previously observed impairment may be due to disruption of the ferroxidase site of the protein since Glu61 is a shared ligand of the ferroxidase and nucleation sites of the protein. This study employed a new nucleation site variant A1 (E64A/E67A) which retains the ferroxidase site ligand Glu61. The data (O-2 uptake, iron binding, and conventional and stopped-flow kinetics measurements) show that variant A I retains a completely functional ferroxidase site and has iron oxidation and mineralization properties similar to those of the wild-type human H-chain protein. Thus, in contrast to previously published literature, this study demonstrates that the putative "nucleation site" does not play an important role in iron uptake or mineralization in H-chain ferritin.