Solution structure of the bacterial frataxin ortholog, CyaY: Mapping the iron binding sites
Solution structure of the bacterial frataxin ortholog, CyaY: Mapping the iron binding sites
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DOI：
10.1016/j.str.2004.08.012
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发表时间：
2004-11-01
期刊：
影响因子：
5.7
通讯作者：
Pastore, A
中科院分区：
文献类型：
--
作者：
Nair, M;Adinolfi, S;Pastore, A
CyaY 是 frataxin 的细菌直系同源物，frataxin 是一种小型线粒体铁结合蛋白，被认为参与铁硫簇的形成。 frataxin 功能的丧失会导致神经退行性疾病弗里德赖希共济失调。我们已经解决了 CyaY 的溶液结构，并使用结构信息将铁结合到蛋白质表面上。野生型 CyaY 与突变体的行为比较表明，具有确定化学计量的特异性结合不需要聚集，并且承载 Fe2+ 和 Fe3+ 的主要结合位点占据分子的高阴离子表面。这种功能在物种间是保守的，因为人 frataxin 的相应区域也能够结合铁，尽管亲和力较弱。 CyaY 上存在二级结合位点，但 frataxin 上没有，暗示可能存在聚合机制。我们提出的突变可能有助于进一步了解 frataxin 的功能。
CyaY is the bacterial ortholog of frataxin, a small mitochondrial iron binding protein thought to be involved in iron sulphur cluster formation. Loss of frataxin function leads to the neurodegenerative disorder Friedreich's ataxia. We have solved the solution structure of CyaY and used the structural information to map iron binding onto the protein surface. Comparison of the behavior of wild-type CyaY with that of a mutant indicates that specific binding with a defined stoichiometry does not require aggregation and that the main binding site, which hosts both Fe2+ and Fe3+, occupies a highly anionic surface of the molecule. This function is conserved across species since the corresponding region of human frataxin is also able to bind iron, albeit with weaker affinity. The presence of secondary binding sites on CyaY, but not on frataxin, hints at a possible polymerization mechanism. We suggest mutations that may provide further insights into the frataxin function.