Iron-Sulfur (Fe/S) Protein Biogenesis: Phylogenomic and Genetic Studies of A-Type Carriers

Abstract

Iron sulfur (Fe/S) proteins are ubiquitous and participate in multiple biological processes, from photosynthesis to DNA repair. Iron and sulfur are highly reactive chemical species, and the mechanisms allowing the multiprotein systems ISC and SUF to assist Fe/S cluster formation in vivo have attracted considerable attention. Here, A-Type components of these systems (ATCs for A-Type Carriers) are studied by phylogenomic and genetic analyses. ATCs that have emerged in the last common ancestor of bacteria were conserved in most bacteria and were acquired by eukaryotes and few archaea via horizontal gene transfers. Many bacteria contain multiple ATCs, as a result of gene duplication and/or horizontal gene transfer events. Based on evolutionary considerations, we could define three subfamilies: ATC-I, -II and -III. Escherichia coli, which has one ATC-I (ErpA) and two ATC-IIs (IscA and SufA), was used as a model to investigate functional redundancy between ATCs in vivo. Genetic analyses revealed that, under aerobiosis, E. coli IscA and SufA are functionally redundant carriers, as both are potentially able to receive an Fe/S cluster from IscU or the SufBCD complex and transfer it to ErpA. In contrast, under anaerobiosis, redundancy occurs between ErpA and IscA, which are both potentially able to receive Fe/S clusters from IscU and transfer them to an apotarget. Our combined phylogenomic and genetic study indicates that ATCs play a crucial role in conveying ready-made Fe/S clusters from components of the biogenesis systems to apotargets. We propose a model wherein the conserved biochemical function of ATCs provides multiple paths for supplying Fe/S clusters to apotargets. This model predicts the occurrence of a dynamic network, the structure and composition of which vary with the growth conditions. As an illustration, we depict three ways for a given protein to be matured, which appears to be dependent on the demand for Fe/S biogenesis.

Specialized Function of Yeast Isa1 and Isa2 Proteins in the Maturation of Mitochondrial [4Fe-4S] Proteins

“…They are related to the ubiquitous "A-type" ISC assembly factors from bacteria and other eukaryotes (21) and interact with the ISC assembly protein Iba57 (22). In contrast to most other ISC components, Isa1 and Isa2 are not required for cell viability, but low levels of either protein induce virtually identical phenotypes, including respiratory incompetence and glutamate-lysine auxotrophy, demonstrating their involvement in cellular ISC assembly (23)(24)(25).…”

“…Deletion of Iba57 elicits similar phenotypes as the lack of either Isa1 or Isa2 (22). In bacteria, A-type ISC proteins are diverse and widespread (3,6,21). Escherichia coli harbors three canonical A-type proteins, IscA, SufA, and ErpA, and the non-canonical NfuA.…”

“…These phenotypes frequently aggravate under special growth conditions, such as iron limitation or oxidative stress, and are linked to the loss of function of crucial cellular Fe/S proteins (3, 21, 26 -33). Canonical A-type ISC proteins contain three highly conserved cysteine residues in two segments close to the terminus that are essential for function in vivo (21,23,25,30). These residues are part of a flexible structure that was predicted to bind iron or an Fe/S cluster (34,35).…”

Identification of medaka magnetoreceptor and cryptochromes

“…Unlike cry, which has already been reported to have other important functions such as circadian rhythm resetting and photosensitivity (Zhu et al, 2008;Chaves et al, 2011), the potential function of magr is to be explored. Since magr is the homologue of bacterial iron-sulfur cluster assembly Isca1, which is evolutionarily highly conserved and found in prokaryotic and eukaryotic organisms for the biogenesis of iron-sulfur cluster across species (Zheng et al, 1998;Schwartz et al, 2001;Vinella et al, 2009), it is predictable that magr may also have similar roles. For example, Nilsson et al have reported that Isca1 knockdown in zebrafish results in anemia (Nilsson et al, 2009).…”

Du fer et du soufre dans les protéines

“…De fait, un mutant de E. coli ne possédant ni SUF ni ISC n'est pas viable parce qu'il ne produit pas assez d'IPP. Cela a été démontré en apportant dans un tel mutant la voie de biosynthèse des IPP eucaryote, qui n'inclut pas de protéines à Fe-S et dépend du mévalonate comme substrat [31,34]. La possibilité de supprimer (dans certaines conditions de croissance) les défauts dus à l'absence des systèmes ISC et SUF par l'apport de gènes eucaryotes permettant la synthèse des IPP, a ouvert la voie à une approche géné-tique des rôles respectifs des systèmes ISC et SUF.…”