Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6AS, UK.
Angew Chem Int Ed Engl. 2024 Apr 15;63(16):e202401379. doi: 10.1002/anie.202401379. Epub 2024 Mar 12.
Ferritins are multimeric cage-forming proteins that play a crucial role in cellular iron homeostasis. All H-chain-type ferritins harbour a diiron site, the ferroxidase centre, at the centre of a 4 α-helical bundle, but bacterioferritins are unique in also binding 12 hemes per 24 meric assembly. The ferroxidase centre is known to be required for the rapid oxidation of Fe during deposition of an immobilised ferric mineral core within the protein's hollow interior. In contrast, the heme of bacterioferritin is required for the efficient reduction of the mineral core during iron release, but has little effect on the rate of either oxidation or mineralisation of iron. Thus, the current view is that these two cofactors function in iron uptake and release, respectively, with no functional overlap. However, rapid electron transfer between the heme and ferroxidase centre of bacterioferritin from Escherichia coli was recently demonstrated, suggesting that the two cofactors may be functionally connected. Here we report absorbance and (magnetic) circular dichroism spectroscopies, together with in vitro assays of iron-release kinetics, which demonstrate that the ferroxidase centre plays an important role in the reductive mobilisation of the bacterioferritin mineral core, which is dependent on the heme-ferroxidase centre electron transfer pathway.
铁蛋白是一种多聚体笼状蛋白，在细胞铁稳态中起着至关重要的作用。所有 H 链型铁蛋白都在 4α-螺旋束的中心含有一个二铁中心，即亚铁氧化酶中心，但细菌铁蛋白的独特之处在于每个 24 聚体组装还结合 12 个血红素。已知亚铁氧化酶中心是在蛋白质中空内部固定的三价铁矿物核心内沉积过程中快速氧化 Fe 所必需的。相比之下，细菌铁蛋白的血红素对于在铁释放过程中有效地还原矿物核心是必需的，但对铁的氧化或矿化速率几乎没有影响。因此，目前的观点是这两个辅因子分别在铁的摄取和释放中起作用，没有功能重叠。然而，最近证明了来自大肠杆菌的细菌铁蛋白血红素和亚铁氧化酶中心之间的快速电子转移，这表明这两个辅因子可能在功能上相互连接。在这里，我们报告了吸收光谱和（圆二色性）光谱学，以及体外铁释放动力学测定，这些研究表明亚铁氧化酶中心在细菌铁蛋白矿物核心的还原动员中起着重要作用，这依赖于血红素-亚铁氧化酶中心电子转移途径。
