OLIGOMERIZATION STUDIES OF THE FRIEDRICH'S ATAXIA PROTEIN FRATAXIN

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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.