This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Iron-sulfur (Fe/S) clusters are important cofactors of numerous proteins. Fe/S clusters required a complex set of proteins to become assembled and incorporated into apoproteins in a living cell. The deficiency of Fe/S cluster proteins may cause cell malfunction and even death. In human, there are some diseases related to Fe/S cluster proteins such as X-linked sideroblastic anemia, X-linked sideroblastic anemia with ataxia and Friedreich ataxia. Frataxin, one of the Fe/S cluster assembly proteins has been the subject of intense investigation due to the discovery that frataxin defects are linked to Friedreich 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. In human frataxin, N-terminal region is required for fratxin oligolmerization. Our results suggest that human frataxin forms larger (possibly 48 subunit) complexes. We have got the initial SAXS data for monomeric full-length human frataxin. The SAXS model suggests the extra N-terminal region might involve the interactions with IscU and frataxin oligomerization. We are trying to understand the interactions and functions of frataxin with IscU and IscS. We also like to investigate the protein complex of Fe/S cluster assembly machinery.
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