Iron–Sulfur Proteins: Structure, Function and Biogenesis

Abstract

Iron–sulfur clusters rank among the most versatile protein cofactors. Proteins using Fe–S clusters intervene in many cellular processes in both bacteria and eukaryotes. Fe–S cluster biogenesis has been a research area of intensive investigations in the past decade. The success of Fe–S cluster‐based biology during evolution is indicated by the myriad of processes that depend on Fe–S cluster‐containing proteins. These include basic metabolic, bioenergetics and genetic information‐related processes. Conserved multiprotein systems, called ISC and SUF, have been identified in most living organisms, from bacteria to plant and mammals. They catalyse assembly of clusters and their delivery to the many apoproteins, the activity of which depends on the acquisition of clusters. Recently, their role in bacterial pathogenicity and bacterial resistance to antibiotics was brought to light.

Key Concepts

  • Fe–S clusters are versatile and ubiquitous cofactors.
  • Fe–S cluster biogenesis is catalysed by multiprotein systems.
  • ISC and SUF Fe–S biogenesis systems are conserved in bacterias and eukaryotes.
  • The IscR regulator controls Fe–S cluster homeostasis.
  • The IscR regulator allows bacteria to adapt to various environmental conditions and hosts.
  • Iron external levels modify aminoglycoside resistance of E. coli via its influence on Fe–S biogenesis.

Keywords: iron–sulfur; oxidative stress; iron metabolism; protein homeostasis; bacteria; antibiotic; pathogenicity

Figure 1. Examples of Fe–S clusters. Most frequently found clusters are depicted. Red and yellow balls represent iron (Fe) and sulfur (S) atoms. L1, L2, L3 and L4 stand for ligands. Most frequently found ligands are Cys residues and His residues.
Figure 2. Fe–S cluster assembly and targeting. Genetic organisation and protein coding capacities of the ISC (a) and SUF (c) are shown. Part (b) describes the basic steps common to both ISC and SUF. The same color code is used throughout all three parts for showing proteins contributing to Fe–S biogenesis: cysteine desulfurases (yellow), scaffold (purple) and ATP (adenosine triphosphate)‐hydrolysing components (green), Fe–S carriers (blue) and targets (pink). See text for details.
Figure 3. Regulation of the isc and suf operons in Escherichia coli. Upper part: expression of the suf operon is repressed by the Fe‐bound form of Fur and activated by the apoform of IscR. Not shown is the activation by OxyR, the H2O2‐sensing transcriptional activator. Lower part: expression of the isc operon is repressed by the Fe–S‐bound form of IscR and posttranscriptionally inhibited by the small noncoding RNA (ribonucleic acid), RyhB. The expression of ryhB is repressed by the Fe‐bound form of Fur. See text for details.
Figure 4. The contribution of Fe–S biogenesis to resistance to antibiotics. Upper part: the ISC system targets Fe–S clusters to complex I (9 Fe–S clusters) and complex II (3 Fe–S clusters), thereby generating the proton‐motive force (PMF) that is exploited for aminoglycosides uptake. Lower part: the ISC system targets Fe–S to helicases (DinG and YoaA), glycosylase (MutY) and endonuclease (Nth) (not depicted), which repair DNA (deoxyribonucleic acid) damage inflicted by quinolones.
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Further Reading

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Barras, Frédéric(Jun 2017) Iron–Sulfur Proteins: Structure, Function and Biogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001377]