OLIGOMERIZATION STUDIES OF THE FRIEDRICH'S ATAXIA PROTEIN FRATAXIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 由于发现共济失调蛋白缺陷与弗里德里希共济失调有关，共济失调是一种以神经损伤、心肌病和糖尿病为特征的进行性疾病，因此共济失调蛋白的功能一直是深入研究的主题。 在体内，frataxin通过向亚铁螯合酶提供铁来促进血红素的生物合成，通过与铁-硫支架蛋白IscU的相互作用来组装铁-硫簇，以及修复铁-硫簇如顺乌头酸酶。 Frataxin还在保护免受氧化应激中起主要作用。 在酵母中，铁依赖性寡聚化的共济失调蛋白已被证明形成24亚基复合物，其功能类似于铁蛋白作为铁储存单位。 我们最近的研究结果表明，人类共济失调蛋白形成更大（可能48个亚基）的复合物。 我们要求SAXS时间的形状重建研究的单体和寡聚状态的人共济失调蛋白及其相互作用的iscU支架蛋白。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The function of frataxin has been the subject of intense investigation due to the discovery that frataxin defects are linked to Friedrich ataxia, a progressive disorder characterized by neurological impairment, cardiomyopathy, and diabetes. In vivo, frataxin promotes the biosynthesis of hemes by donating iron to ferrochelatase, the assembly of iron-sulfur clusters through interactions with the iron-sulfur scaffolding protein IscU, and the repair of iron-sulfur clusters such as aconitase. Frataxin also plays a primary role in the protection against oxidative stress. In yeast, Fe-dependent oligomerization of frataxin has been shown to form 24 subunit complexes that may function similarly to ferritin as iron-storage units. Our recent results suggest that human frataxin forms larger (possibly 48 subunit) complexes. We request SAXS time for shape reconstruction studies of the monomeric and oligomeric states of human frataxin and its interaction with the iscU scaffolding protein.