Crystal structure of
            <i>Escherichia coli</i>
            CyaY protein reveals a previously unidentified fold for the evolutionarily conserved frataxin family

Cho, Seung Je; Lee, Myong Gyong; Yang, Jong Oh; Lee, Jae Young; Song, Hyun Kyu; Suh, Se Won

doi:10.1073/pnas.160270897

Cited by 116 publications

(85 citation statements)

References 32 publications

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“…The common biological functions shared by the different frataxin homologs may be mediated by the protein-protein interactions through the negative charge deficient b-sheet side of the structure [31]. Indeed experimental evidences accumulated so far indicate that different frataxin homologs can interact with other proteins as iron-chaperone protein, or as more general regulator of iron metabolism and trafficking in mitochondria [9, and references therein].…”

Section: Discussionmentioning

confidence: 99%

Knockout of frataxin gene causes embryo lethality in Arabidopsis

et al. 2007

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Frataxin is present in mitochondria of all eukaryotes as well as in the cytoplasm of bacteria. In humans, reduced expression of frataxin is associated with Friedreich's ataxia, a recessive inherited neurodegenerative and cardiac disorder leading to reduced life expectancy. Experimental evidences suggest that frataxin acts as an iron-chaperone protein, donating iron to the proteins involved in [Fe-S] cluster assembly and heme synthesis. It also possibly contributes to the process of iron detoxification and storage.The frataxin homolog from Arabidopsis thaliana (AtFH) is a single nuclear-encoded gene targeted to mitochondria and sharing 65% similarity with animal frataxin. In the present work, we show that the knocking out of AtFH gene causes arrest of Arabidopsis embryo development at the globular stage. Consistently with that, we also show by in situ hybridization that AtFH is expressed, in wt Arabidopsis plants, in ovule primordia as well as in embryos at various stages of development, suggesting a key role of plant frataxin during embryogenesis.

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Section: Discussionmentioning

confidence: 99%

Knockout of frataxin gene causes embryo lethality in Arabidopsis

et al. 2007

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“…Mitochondrial localization has been demonstrated for both the human and yeast frataxins [13][14][15]. Interestingly, AtFH possesses an Arg at position 177 as found in other plant and the yeast predicted genes as well as in the bacterial homolog CyaY [16]. In the human frataxin, a His residue involved in iron binding is found at this position [17].…”

Section: Atfh Is a 187 Aa Peptide And Possesses A Mitochondrialmentioning

confidence: 96%

Functional and molecular characterization of the frataxin homolog from Arabidopsis thaliana,

Busi

Zabaleta

Araya³

et al. 2004

FEBS Letters

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Frataxin is a highly conserved protein from bacteria to mammals that has been proposed to participate in iron-sulfur cluster assembly and mitochondrial iron homeostasis. In higher organisms, the frataxin gene is nuclear-encoded and the protein is required for maintenance of normal mitochondrial iron levels and respiration. We describe here AtFH, a plant gene with significant homology to other members of the frataxin family. Plant frataxin has five segments of beta regions and two alpha helices, which are characteristics of human frataxin, as well as a potential N-terminal targeting peptide for the mitochondrial localization. Transcription analysis showed that AtFH is ubiquitously expressed with high levels in flowers. Complementation of a Saccharomyces cerevisiae mutant (Dyfh) lacking the frataxin gene proved that AtFH is a functional protein, because it restored normal rates of respiration, growth and sensitivity to H 2 O 2 of the null mutant. Our results support the involvement of AtFH in mitochondrial respiration and survival during oxidative stress in plants. This is the first report of a functional frataxin gene in plants.

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“…Yeast frataxin (7) shares common sequence and structural features with its human (8) and bacterial counterparts (9). The overall structure of frataxin has a unique fold characterized by a platform of six or seven ␤-sheets and two ␣-helices situated above the plane.…”

mentioning

confidence: 99%

Mrs3p, Mrs4p, and Frataxin Provide Iron for Fe-S Cluster Synthesis in Mitochondria

Zhang

Lyver

Knight

et al. 2006

Journal of Biological Chemistry

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Yeast Mrs3p and Mrs4p are evolutionarily conserved mitochondrial carrier proteins that transport iron into mitochondria under some conditions. Yeast frataxin (Yfh1p), the homolog of the human protein implicated in Friedreich ataxia, is involved in iron homeostasis. However, its precise functions are controversial. Anaerobically grown triple mutant cells (⌬mrs3/4/⌬yfh1) displayed a severe growth defect corrected by in vivo iron supplementation. Because anaerobically grown cells do not synthesize heme, and they do not experience oxidative stress, this growth defect was most likely due to Fe-S cluster deficiency. Fe-S cluster formation was assessed in anaerobically grown cells shifted to air for a brief period. In isolated mitochondria, Fe-S clusters were detected on newly imported yeast ferredoxin precursor and on endogenous aconitase by means of [ 35 S]cysteine labeling and native gel separation. New cluster formation was dependent on iron addition to mitochondria, and the iron concentration dependence was shifted dramatically upward in the ⌬mrs3/4 mutant, indicating a role of Mrs3/4p in iron transport. The frataxin mutant strain lacked protein import capacity because of low mitochondrial membrane potential, although this was partially restored by growth in the presence of high iron. Under these conditions, a kinetic defect in new Fe-S cluster formation was still noted. Import of frataxin into frataxin-minus isolated mitochondria promptly corrected the Fe-S cluster assembly defect without further iron addition. These findings show that Mrs3/4p transports iron into mitochondria, whereas frataxin makes iron already within mitochondria available for Fe-S cluster synthesis.

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Crystal structure of Escherichia coli CyaY protein reveals a previously unidentified fold for the evolutionarily conserved frataxin family

Cited by 116 publications

References 32 publications

Knockout of frataxin gene causes embryo lethality in Arabidopsis

Knockout of frataxin gene causes embryo lethality in Arabidopsis

Functional and molecular characterization of the frataxin homolog from Arabidopsis thaliana,

Mrs3p, Mrs4p, and Frataxin Provide Iron for Fe-S Cluster Synthesis in Mitochondria

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