Lawson D M, Artymiuk P J, Yewdall S J, Smith J M, Livingstone J C, Treffry A, Luzzago A, Levi S, Arosio P, Cesareni G
Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University, Sheffield, UK.
Nature. 1991 Feb 7;349(6309):541-4. doi: 10.1038/349541a0.
Ferritin is important in iron homeostasis. Its twenty-four chains of two types, H and L, assemble as a hollow shell providing an iron-storage cavity. Ferritin molecules in cells containing high levels of iron tend to be rich in L chains, and may have a long-term storage function, whereas H-rich ferritins are more active in iron metabolism. The molecular basis for the greater activity of H-rich ferritins has until now been obscure, largely because the structure of H-chain ferritin has remained unknown owing to the difficulties in obtaining crystals ordered enough for X-ray crystallographic analysis. Here we report the three-dimensional structure of a human ferritin H-chain homopolymer. By genetically engineering a change in the sequence of the intermolecular contact region, we obtained crystals isomorphous with the homologous rat L ferritin and of high enough quality for X-ray diffraction analysis. The X-ray structure of human H ferritin shows a novel metal site embedded within each of its four-helix bundles and we suggest that ferroxidase activity associated with this site accounts for its rapid uptake of iron.
铁蛋白在铁稳态中起着重要作用。它由H和L两种类型的24条链组装成一个中空的外壳，形成一个铁储存腔。细胞中含铁量高的铁蛋白分子往往富含L链，可能具有长期储存功能，而富含H链的铁蛋白在铁代谢中更活跃。富含H链的铁蛋白具有更高活性的分子基础至今仍不清楚，主要是因为由于难以获得足够有序的晶体用于X射线晶体学分析，H链铁蛋白的结构一直未知。在此，我们报道了一种人铁蛋白H链同聚物的三维结构。通过基因工程改变分子间接触区域的序列，我们获得了与同源大鼠L铁蛋白同晶且质量足以进行X射线衍射分析的晶体。人H铁蛋白的X射线结构显示在其每个四螺旋束中都嵌入了一个新的金属位点，我们认为与该位点相关的铁氧化酶活性解释了其对铁的快速摄取。
