Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria, 3800, Australia.
Biochem J. 2010 Feb 9;426(2):e1-3. doi: 10.1042/BJ20091959.
What are the structural implications for iron binding by frataxin, the mitochondrial protein whose decreased expression results in Friedreich's ataxia? Though frataxin has been shown to be essential for proper handling of iron within mitochondria (e.g. for iron-sulfur cluster and haem biosynthesis), its exact molecular function remains unclear. In this issue of the Biochemical Journal, Correia and colleagues. investigate the relationship between structure and function at the putative iron-binding site of Yfh1 (yeast frataxin). Using a host of Yfh1 combination point mutants, the authors observe that the presence of a semi-conserved pocket of negative charge within the 'acidic ridge' region (thought to be responsible for iron binding) only mildly enhances Yfh1's ability to bind iron, though it does significantly increase the protein's structural flexibility. The general emerging view is that frataxin's keystone role in mitochondrial iron metabolism depends on iron binding. This appears to have downstream effects on protein-protein interactions that are crucial for frataxin function. The current results reveal a somewhat delicate relationship between iron binding and structural plasticity that may help unravel the enigma of frataxin's metabolic roles.
铁结合对 frataxin（一种线粒体蛋白，其表达减少会导致弗里德里希共济失调）有何结构影响？尽管已经表明 frataxin 对于线粒体中铁的正确处理（例如铁-硫簇和血红素生物合成）是必不可少的，但它的确切分子功能仍不清楚。在本期《生物化学杂志》中，Correia 及其同事研究了假定的酵母 frataxin（Yfh1）铁结合位点的结构与功能之间的关系。作者使用一系列 Yfh1 组合点突变体观察到，在“酸性脊”区域（被认为负责铁结合）内存在一个半保守的负电荷口袋，仅略微增强了 Yfh1 结合铁的能力，尽管它确实显著增加了蛋白质的结构灵活性。普遍的观点是，frataxin 在线粒体铁代谢中的关键作用取决于铁结合。这似乎对对于 frataxin 功能至关重要的蛋白质-蛋白质相互作用产生了下游影响。目前的结果揭示了铁结合与结构可塑性之间的一种微妙关系，这可能有助于解开 frataxin 代谢作用的谜团。
