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Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery

Iron-Sulphur clusters, essential cofactors needed for the activity of many different enzymes, are assembled by conserved protein machineries inside bacteria and mitochondria. As the architecture of the human machinery remains undefined, we co-expressed in E. coli four proteins involved in the initial step of Fe-S cluster synthesis: FXN42-210 (iron donor), [NFS1]-[ISD11] (sulfur donor), and ISCU (scaffold upon which new clusters are assembled). We purified a stable, active complex consisting of all four proteins with 1:1:1:1 stoichiometry.

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