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.Proteins containing iron-sulfur clusters possess important electron transfer, catalytic, and regulatory functions, but the cellular mechanism by which Fe/S-clusters are formed and repaired is not known. Recently, a combination of biochemical and genetic studies have implicated several novel proteins in Fe/S-cluster biogenesis. In bacteria these proteins are encoded in a conserved gene cluster that includes three iron sulfur cluster assembly genes (IscS, IscU, IscA), two heat shock cognate chaperone genes (hscA and hscB). We have overexpressed and purified each of the corresponding proteins from E. coli and have performed a variety of biochemical studies to investigate their roles in the assembly of Fe/S-clusters and the incorporation of Fe/S-clusters into proteins. We have previously reported the x-ray structure of the HscB and IscS proteins based on data collected at SSRL. In addition, we have recently obtained diffraction quality crystals for the remaining proteins (or fragments of them) that participate in Fe-S cluster formation (HscA, IscA, and IscU). These studies will provide a better understanding of molecular mechanisms involved in the assembly of Fe/S clusters. Furthermore, it appears likely that a conserved mechanism of Fe/S-protein assembly occurs in eukaryotes, and the findings of these studies may provide new insights into the molecular basis of human diseases such as those associated with mitochondrial myopathies.
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