STRUCTURE AND MECHANISTIC STUDIES OF HUMAN FE-S CLUSTER BIOSYNTHESIS

这个子项目是众多研究子项目之一

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. Friedreich?s ataxia is the most common inherited ataxia and results from the loss of function for the protein frataxin. Frataxin has been implicated in iron homeostasis and, particularly, in iron-sulfur protein biosynthesis. Frataxin specifically interacts with the scaffold protein IscU and delivers iron for iron-sulfur cluster assembly. Although the structure of human frataxin is known, the frataxin iron binding site, the structure of human IscU, and details for the frataxin:IscU complex remain elusive. In addition, clinical mutants of human frataxin have been identified (such as D122Y, G130V, I154F, W155R) but not structurally or functionally characterized. The objectives of this proposal are to determine crystallographic structures of (i) human frataxin with iron; (ii) clinical mutants of frataxin; (iii) human IscU; and (iv) the frataxin:IscU complex.