Nair Margie, Adinolfi Salvatore, Pastore Chiara, Kelly Geoff, Temussi Pierandrea, Pastore Annalisa
Division of Molecular Structure, The Ridgeway, London, NW7 1AA, United Kingdom.
Structure. 2004 Nov;12(11):2037-48. doi: 10.1016/j.str.2004.08.012.
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 Fe(2+) and Fe(3+), 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.
CyaY是铁调素（frataxin）在细菌中的同源物，铁调素是一种小的线粒体铁结合蛋白，被认为参与铁硫簇的形成。铁调素功能丧失会导致神经退行性疾病弗里德赖希共济失调。我们解析了CyaY的溶液结构，并利用该结构信息将铁结合定位到蛋白质表面。野生型CyaY与突变体行为的比较表明，具有确定化学计量比的特异性结合并不需要聚集，且同时容纳Fe(2+)和Fe(3+)的主要结合位点占据了分子的一个高度阴离子表面。由于人类铁调素的相应区域也能够结合铁，尽管亲和力较弱，但这种功能在物种间是保守的。CyaY上存在二级结合位点，而铁调素上没有，这暗示了一种可能的聚合机制。我们提出了一些突变，这些突变可能会为深入了解铁调素的功能提供进一步的线索。
