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Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS

Adinolfi, Salvatore and Iannuzzi, Clara and Prischi, Filippo and Pastore, Chiara and Iametti, Stefania and Martin, Stephen R and Bonomi, Franco and Pastore, Annalisa (2009) 'Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS.' Nature Structural & Molecular Biology, 16 (4). pp. 390-396. ISSN 1545-9993

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Frataxin is an essential mitochondrial protein whose reduced expression causes Friedreich's ataxia (FRDA), a lethal neurodegenerative disease. It is believed that frataxin is an iron chaperone that participates in iron metabolism. We have tested this hypothesis using the bacterial frataxin ortholog, CyaY, and different biochemical and biophysical techniques. We observe that CyaY participates in iron-sulfur (Fe-S) cluster assembly as an iron-dependent inhibitor of cluster formation, through binding to the desulfurase IscS. The interaction with IscS involves the iron binding surface of CyaY, which is conserved throughout the frataxin family. We propose that frataxins are iron sensors that act as regulators of Fe-S cluster formation to fine-tune the quantity of Fe-S cluster formed to the concentration of the available acceptors. Our observations provide new perspectives for understanding FRDA and a mechanistic model that rationalizes the available knowledge on frataxin. © 2009 Nature America, Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Escherichia coli; Iron; Macromolecular Substances; Carbon-Sulfur Lyases; Bacterial Proteins; Escherichia coli Proteins; Iron-Binding Proteins; Chromatography, Gel; Protein Interaction Mapping; Protein Binding; Kinetics; Models, Molecular; Protein Interaction Domains and Motifs
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 04 Feb 2016 11:49
Last Modified: 18 Aug 2022 11:31

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