Understanding the binding properties of an unusual metal-binding protein - a study of bacterial frataxin
Understanding the binding properties of an unusual metal-binding protein - a study of bacterial frataxin
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DOI：
10.1111/j.1742-4658.2007.05946.x
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发表时间：
2007-08-01
期刊：
影响因子：
5.4
通讯作者：
Pastore, Annalisa
中科院分区：
文献类型：
--
作者：
Pastore, Chiara;Franzese, Marisa;Pastore, Annalisa
小线粒体蛋白卵黄蛋白的缺乏导致弗里德赖希共济失调，这是一种严重的神经退行性病理。在整个进化过程中高度保守的Frataxin被认为参与了Fe-S簇形成等过程。独立证据表明，它直接结合铁，尽管具有非常明显的特征和低亲和力。在这里，我们利用核磁共振和x射线晶体学进行了广泛的研究CyaY（细菌同源物）与不同二价和三价阳离子的结合特性。我们证明该蛋白具有低阳离子特异性，并且含有多个结合位点，能够以低亲和力螯合二价和三价金属。结合不涉及空腔或口袋，而是暴露的谷氨酸和天冬氨酸，当没有组氨酸和/或半胱氨酸的辅助时，这些残基在铁螯合中是不寻常的。我们已经介绍了这种通过静电机制在相对大的区域上结合阳离子的能力如何成为蛋白质功能的宝贵资产。
Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe-S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. Here, we have carried out an extensive study of the binding properties of CyaY, the bacterial ortholog of frataxin, to different divalent and trivalent cations, using NMR and X-ray crystallography. We demonstrate that the protein has low cation specificity and contains multiple binding sites able to chelate divalent and trivalent metals with low affinity. Binding does not involve cavities or pockets, but exposed glutamates and aspartates, which are residues that are unusual for iron chelation when not assisted by histidines and/or cysteines. We have related how such an ability to bind cations on a relatively large area through an electrostatic mechanism could be a valuable asset for protein function.