From Iron and Cysteine to Iron-Sulfur Clusters: the Biogenesis Protein Machineries.

Abstract

This review describes the two main systems, namely the Isc (iron-sulfur cluster) and Suf (sulfur assimilation) systems, utilized by Escherichia coli and Salmonella for the biosynthesis of iron-sulfur (Fe-S) clusters, as well as other proteins presumably participating in this process. In the case of Fe-S cluster biosynthesis, it is assumed that the sulfur atoms from the cysteine desulfurase end up at cysteine residues of the scaffold protein, presumably waiting for iron atoms for cluster assembly. The review discusses the various potential iron donor proteins. For in vitro experiments, in general, ferrous salts are used during the assembly of Fe-S clusters, even though this approach is unlikely to reflect the physiological conditions. The fact that sulfur atoms can be directly transferred from cysteine desulfurases to scaffold proteins supports a mechanism in which the latter bind sulfur atoms first and iron atoms afterwards. In E. coli, fdx gene inactivation results in a reduced growth rate and reduced Fe-S enzyme activities. Interestingly, the SufE structure resembles that of IscU, strengthening the notion that the two proteins share the property of acting as acceptors of sulfur atoms provided by cysteine desulfurases. Several other factors have been suggested to participate in cluster assembly and repair in E. coli and Salmonella. Most of them were identified by their abilities to act as extragenic and/or multicopy suppressors of mutations in Fe-S cluster metabolism, while others possess biochemical properties that are consistent with a role in Fe-S cluster biogenesis.