Effector Role Reversal during Evolution: The Case of Frataxin in Fe鈥揝 Cluster Biosynthesis

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• 作者：Jennifer Bridwell-Rabb ; Clara Iannuzzi ; Annalisa Pastore ; David P. Barondeau
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：March 27, 2012
• 年：2012
• 卷：51
• 期：12
• 页码：2506-2514
• 全文大小：430K
• 年卷期：v.51,no.12(March 27, 2012)
• ISSN：1520-4995

文摘

Human frataxin (FXN) has been intensively studied since the discovery that the FXN gene is associated with the neurodegenerative disease Friedreich鈥檚 ataxia. Human FXN is a component of the NFS1-ISD11-ISCU2-FXN (SDUF) core Fe鈥揝 assembly complex and activates the cysteine desulfurase and Fe鈥揝 cluster biosynthesis reactions. In contrast, the Escherichia coli FXN homologue CyaY inhibits Fe鈥揝 cluster biosynthesis. To resolve this discrepancy, enzyme kinetic experiments were performed for the human and E. coli systems in which analogous cysteine desulfurase, Fe鈥揝 assembly scaffold, and frataxin components were interchanged. Surprisingly, our results reveal that activation or inhibition by the frataxin homologue is determined by which cysteine desulfurase is present and not by the identity of the frataxin homologue. These data are consistent with a model in which the frataxin-less Fe鈥揝 assembly complex exists as a mixture of functional and nonfunctional states, which are stabilized by binding of frataxin homologues. Intriguingly, this appears to be an unusual example in which modifications to an enzyme during evolution inverts or reverses the mode of control imparted by a regulatory molecule.