Calculation of Iron Transport through Human H-chain Ferritin
Calculation of Iron Transport through Human H-chain Ferritin
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DOI：
10.1021/jp500198u
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发表时间：
2014-09-04
影响因子：
2.9
通讯作者：
Coalson, Rob D.
中科院分区：
文献类型：
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作者：
Laghaei, Rozita;Kowallis, William;Coalson, Rob D.
用三维Poisson-Nernst-Planck电扩散模型计算了Fe2+离子从细胞质通过铁蛋白壳层三重孔的内流，输入参数包括孔结构和从全原子分子动力学(MD)模拟中提取的Fe2+离子的扩散系数分布。这些计算成功地再现了Fe2+通过铁蛋白涂层的时间的实验估计，铁蛋白涂层在毫秒级上，因此太长了，无法通过全原子MD直接模拟。这也比跨越离子通道的标准膜中离子传输的典型时间尺度长得多，标准膜的孔具有与铁蛋白3倍孔相似的结构。Fe2+通过铁蛋白孔转运的缓慢时间尺度可以追溯到两个区别于标准离子通道的特征，即(I)生理条件下细胞质Fe2+浓度非常低和(Ii)铁蛋白孔内离子的内扩散系数非常小，这是由于Fe2+的二价性和铁蛋白孔内部狭窄几何障碍周围的两个带负电荷的氨基酸环所致。
Influx of ferrous ions from the cytoplasm through 3-fold pores in the shell of ferritin protein is computed using a 3-dimensional Poisson-Nernst-Planck electrodiffusion model, with inputs such as the pore structure and the diffusivity profile of permeant Fe2+ ions extracted from all-atom molecular dynamics (MD) simulations. These calculations successfully reproduce experimental estimates of the transit time of Fe2+ through the ferritin coat, which is on the millisecond time scale and hence much too long to be directly simulated via all-atom MD. This is also much longer than the typical time scale for ion transit in standard membrane spanning ion channels whose pores bear structural similarity to that of the 3-fold ferritin pore. The slow time scale for Fe2+ transport through ferritin pores is traced to two features that distinguish the ferritin pore system from standard ion channels, namely, (i) very low concentration of cytoplasmic Fe2+ under physiological conditions and (ii) very small internal diffusion coefficients for ions inside the ferritin pore resulting from factors that include the divalent nature of Fe2+ and two rings of negatively charged amino acids surrounding a narrow geometric obstruction within the ferritin pore interior.