Elucidating the Molecular Function of Human BOLA2 in GRX3-Dependent Anamorsin Maturation Pathway

Banci, Lucia; Camponeschi, Francesca; Ciofi‐Baffoni, Simone; Muzzioli, Riccardo

doi:10.1021/jacs.5b10592

Cited by 68 publications

(92 citation statements)

References 48 publications

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“…Several studies in yeast have underscored the critical role of cytosolic monothiol glutaredoxins and their BolA-binding partners in iron homeostasis (26,33,48), and a recent in vitro study of human Glrx3 and BolA2 characterized their capacity to bind and transfer [2Fe-2S] clusters (14,27). Here, we show that Glrx3 and BolA2 form a complex in human cells and that complex formation is highly dependent on coordination of bridging Fe-S clusters.…”

Section: Discussionmentioning

confidence: 52%

“…(43,47). In vitro work also demonstrates the transfer of [2Fe-2S] clusters from Glrx3 homodimers and Glrx3⅐BolA2 complexes to Ciapin1 (27,28). These studies raise the possibility that [2Fe-2S] cluster exchange could occur between Ciapin1, Glrx3, and BolA2 in mammalian cells.…”

Section: Figure 6 Ciao1 Binds Glrx3 But Is Not Required For Glrx3⅐bomentioning

confidence: 79%

“…BolA1 proteins are largely uncharacterized. In vitro, both yeast and human BolA2 form complexes with Glrx3 that contain one or two bridging [2Fe-2S] clusters that are coordinated by a conserved histidine residue in BolA2 (10,13,14,26 hetero-oligomers can all be transferred to Ciapin1, an Fe-S protein involved in early steps of cytosolic Fe-S cluster assembly (27,28). However, it is not clear which, if any, of these transfer reactions can occur in a cellular context.…”

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confidence: 99%

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A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery

Frey

Palenchar

Wildemann

et al. 2016

Journal of Biological Chemistry

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Cells contain hundreds of proteins that require iron cofactors for activity. Iron cofactors are synthesized in the cell, but the pathways involved in distributing heme, iron-sulfur clusters, and ferrous/ferric ions to apoproteins remain incompletely defined. In particular, cytosolic monothiol glutaredoxins and BolA-like proteins have been identified as [2Fe-2S]-coordinating complexes in vitro and iron-regulatory proteins in fungi, but it is not clear how these proteins function in mammalian systems or how this complex might affect Fe-S proteins or the cytosolic Fe-S assembly machinery. To explore these questions, we use quantitative immunoprecipitation and live cell proximitydependent biotinylation to monitor interactions between Glrx3, BolA2, and components of the cytosolic iron-sulfur cluster assembly system. We characterize cytosolic Glrx3⅐BolA2 as a Although hundreds of cellular proteins require iron-containing cofactors for activity (1), the machinery responsible for distributing these cofactors remains relatively obscure. Separate systems must exist for both the mitochondrial and the cytosolic/nuclear compartments and systems must selectively distribute ferrous iron ions, iron-sulfur (Fe-S) centers, and heme.Recent studies indicate that the poly(rC)-binding proteins are involved in the distribution of ferrous iron to ferritin, the principal iron storage protein, and to mono-and dinuclear iron enzymes in the cytosol of mammalian cells (2-4). Studies in both bakers' yeast and vertebrates indicate that many proteins are involved in the assembly and distribution of Fe-S clusters in the cytosol (5-7). These proteins are structurally and functionally conserved across many species. One protein class, the monothiol glutaredoxins, has been functionally implicated in the trafficking of both ionic iron and Fe-S clusters (8 -12).Monothiol glutaredoxins are members of the thioredoxin (Trx) 3 -fold family of proteins. Most members of the Trx family utilize a dithiol active site to catalyze the oxido-reduction of thiol-disulfide residues. In contrast, monothiol glutaredoxins contain a Cys-Gly-Phe-Ser active site that lacks catalytic activity and instead coordinates a [2Fe-2S] cluster via the active site cysteine and the sulfhydryl residue of a molecule of glutathione, which is non-covalently bound adjacent to the glutaredoxin active site (10,(13)(14)(15). In vitro analysis of this Fe-S-containing species indicates that two glutathione-bound glutaredoxin proteins can coordinate a single [2Fe-2S] cluster as a bridging complex. In eukaryotes, distinct monothiol glutaredoxins are expressed in the mitochondria and cytosol. Genetic evidence suggests that mitochondrial glutaredoxins are involved in the transfer of newly assembled Fe-S clusters to recipient apoproteins (8,9,16,17). Cytosolic monothiol glutaredoxins differ from their mitochondrial paralogs in that they contain an amino-terminal Trx-like domain followed by one or more glutaredoxin domains. Studies in fungi suggest these proteins are involved in iron homeostasis.Th...

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Section: Discussionmentioning

confidence: 52%

Section: Figure 6 Ciao1 Binds Glrx3 But Is Not Required For Glrx3⅐bomentioning

confidence: 79%

mentioning

confidence: 99%

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A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery

Frey

Palenchar

Wildemann

et al. 2016

Journal of Biological Chemistry

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“…The assembly of Fe-S clusters onto Dre2 was reported to be independent of CIA components, a mechanism referred to as "unprecedented for a non-scaffold Fe-S protein" (Netz et al, 2010). Studies by Banci et al have recently elucidated not one, but two alternative maturation pathways for Dre2 in the cytosol (Banci et al, 2015a(Banci et al, , 2015b.…”

Section: Fe-s Assembly Machineriesmentioning

confidence: 99%

“…GRX3 is an in vivo Dre2 binding partner in both yeast (Rual et al, 2005) and mouse in the cytosol. A specific interaction between the N-terminal domains of the two proteins promotes the transfer of two 2Fe-2S clusters from GRX3 (Banci et al, 2015b) or GRX3-BOLA2 (Banci et al, 2015a) to Dre2. It was suggested that these two pathways may be operative under normal and oxidative stress conditions, respectively (Banci et al, 2015a).…”

Section: Fe-s Assembly Machineriesmentioning

confidence: 99%

Emerging links between iron-sulfur clusters and 5-methylcytosine base excision repair in plants

Buzas

2016

Genes Genet. Syst.

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Iron-sulfur (Fe-S) clusters are ancient cofactors present in all kingdoms of life. Both the Fe-S cluster assembly machineries and target apoproteins are distributed across different subcellular compartments. The essential function of Fe-S clusters in nuclear enzymes is particularly difficult to study. The base excision repair (BER) pathway guards the integrity of DNA; enzymes from the DEMETER family of DNA glycosylases in plants are Fe-S cluster-dependent and extend the BER repertowere to excision of 5-methylcytosine (5mC). Recent studies in plants genetically link the majority of proteins from the cytosolic Fe-S cluster biogenesis (CIA) pathway with 5mC BER and DNA repair. This link can now be further explored. First, it opens new possibilities for understanding how Fe-S clusters participate in 5mC BER and related processes. I describe DNA-mediated charge transfer, an Fe-S cluster-based mechanism for locating base lesions with high efficiency, which is used by bacterial DNA glycosylases encoding Fe-S cluster binding domains that are also conserved in the DEMETER family. Second, because detailed analysis of the mutant phenotype of CIA proteins relating to 5mC BER revealed that they formed two groups, we may also gain new insights into both the composition of the Fe-S assembly pathway and the biological contexts of Fe-S proteins.

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Cytosolic iron–sulfur cluster transfer—a proposed kinetic pathway for reconstitution of glutaredoxin 3

2016

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Iron-sulfur clusters are ubiquitously conserved and play essential cellular roles. The mechanism of Fe-S cluster biogenesis involves multiple proteins in a complex pathway. Cluster biosynthesis primarily occurs in the mitochondria, but key Fe-S proteins also exist in the cytosol. One such protein, glutaredoxin 3 (Grx3), is involved in iron regulation, sensing and mediating [2Fe-2S] cluster delivery to cytosolic protein targets, but the cluster donor for cytosolic Grx3 has not been elucidated. Herein, we delineate the kinetic transfer of [2Fe-2S] clusters into Grx3 from potential cytosolic carrier/scaffold proteins, IscU and Nfu, to evaluate a possible model for Grx3 reconstitution in vivo.

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Elucidating the Molecular Function of Human BOLA2 in GRX3-Dependent Anamorsin Maturation Pathway

Cited by 68 publications

References 48 publications

A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery

A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery

Emerging links between iron-sulfur clusters and 5-methylcytosine base excision repair in plants

Cytosolic iron–sulfur cluster transfer—a proposed kinetic pathway for reconstitution of glutaredoxin 3

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