title: Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS.
abstract: 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.
authors.affiliation: National Institute for Medical Research, The Ridgeway, London, UK.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Adinolfi
authors.forename: Clara
authors.initials: C
authors.lastname: Iannuzzi
authors.forename: Filippo
authors.initials: F
authors.lastname: Prischi
authors.forename: Chiara
authors.initials: C
authors.lastname: Pastore
authors.forename: Stefania
authors.initials: S
authors.lastname: Iametti
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Martin
authors.forename: Franco
authors.initials: F
authors.lastname: Bonomi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D013437:Carbon-Sulfur Lyases / Q000378:metabolism*; D002850:Chromatography, Gel; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping
chemical_list: D001426:Bacterial Proteins; C120906:CyaY protein, E coli; D029968:Escherichia coli Proteins; D033862:Iron-Binding Proteins; D046911:Macromolecular Substances; D007501:Iron; D013437:Carbon-Sulfur Lyases; C080546:cysteine desulfurase