title: Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu.
abstract: Friedreich ataxia is caused by reduced activity of frataxin, a conserved iron-binding protein of the mitochondrial matrix, thought to supply iron for formation of Fe-S clusters on the scaffold protein Isu. Frataxin binds Isu in an iron-dependent manner in vitro. However, the biological relevance of this interaction and whether in vivo the interaction between frataxin and Isu is mediated by adaptor proteins is a matter of debate. Here, we report that alterations of conserved, surface-exposed residues of yeast frataxin, which have deleterious effects on cell growth, impair Fe-S cluster biogenesis and interaction with Isu while altering neither iron binding nor oligomerization. Our results support the idea that the surface of the beta-sheet, adjacent to the acidic, iron binding ridge, is important for interaction of Yfh1 with the Fe-S cluster scaffold and point to a critical role for frataxin in Fe-S cluster biogenesis.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Craig
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D004579:Electron Transport; D005621:Friedreich Ataxia / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D015854:Up-Regulation / Q000235:genetics; D000096923:Frataxin
chemical_list: D000596:Amino Acids; D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000096923:Frataxin; C121520:ISU1 protein, S cerevisiae