Iron-sulfur cluster biosynthesis

Abstract

Iron-sulfur (Fe-S) clusters are present in more than 200 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Hence the process of Fe-S cluster biosynthesis is essential to almost all forms of life and is remarkably conserved in prokaryotic and eukaryotic organisms. Three distinct types of Fe-S cluster assembly machinery have been established in bacteria, termed the NIF, ISC and SUF systems, and, in each case, the overall mechanism involves cysteine desulfurase-mediated assembly of transient clusters on scaffold proteins and subsequent transfer of pre-formed clusters to apo proteins. A molecular level understanding of the complex processes of Fe-S cluster assembly and transfer is now beginning to emerge from the combination of in vivo and in vitro approaches. The present review highlights recent developments in understanding the mechanism of Fe-S cluster assembly and transfer involving the ubiquitous U-type scaffold proteins and the potential roles of accessory proteins such as Nfu proteins and monothiol glutaredoxins in the assembly, storage or transfer of Fe-S clusters.

Figure 1. Organization of genes in selected bacterial nif, isc, and suf operons

Av,Azotobacter vinelandii; Ec, Escherichia coli; Tm, Thermotoga maritima.

Figure 2. Primary sequence comparisons for U-type scaffold proteins

Numbers refer to the conserved cysteines in the Azotobacter vinelandii IscU sequence. Fully conserved residues are shaded in black. The LPPVK sequences that are required for IscU interactions with HscA and the histidine (NifU and IscU) and lysine (SufU) residues in the cluster binding pocket are shaded in grey. Av,Azotobacter vinelandii; Ec, Escherichia coli; Hi, Haemophilus influenzae; At, Arabidopsis thaliana; Sc, Saccharomyces cerevisiae; Hs, Homo sapiens; Sp, Streptococcus pyogenes; Bs, Bacillus subtilis; Tm, Thermotoga maritima.

Figure 3

Working hypothesis for the mechanism of IscS-mediated [Fe₂S₂]²⁺ and [Fe₄S4]²⁺ cluster assembly on IscU and transfer to the apo forms of acceptor proteins.