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Acidic residues of yeast frataxin have an essential role in Fe–S cluster assembly
Author(s) -
Foury Françoise,
Pastore Annalisa,
Trincal Mathieu
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400881
Subject(s) - frataxin , iron binding proteins , alanine , biochemistry , yeast , iron–sulfur cluster , saccharomyces cerevisiae , chemistry , scaffold protein , lysine , biophysics , chaperone (clinical) , oxidative phosphorylation , mitochondrion , amino acid , biology , enzyme , gene , signal transduction , medicine , pathology
Friedreich ataxia is caused by decreased levels of frataxin, a mitochondrial acidic protein that is assumed to act as chaperone in the assembly of Fe–S clusters on the scaffold Isu protein. Frataxin has the in vitro capacity to form iron‐loaded multimers, which also suggests an iron storage function. It has been reported that alanine substitution of residues in an acidic ridge of yeast frataxin (Yfh1) elicits loss of iron binding in vitro but has no effect on Fe–S cluster synthesis in vivo . Here, we show that a marked change in the electrostatic properties of a specific region of Yfh1 surface—by substituting two or four acidic residues by lysine or alanine, respectively—impairs Fe–S cluster assembly, weakens the interaction between Yfh1 and Isu1, and increases oxidative damage. Therefore, the acidic ridge is essential for the Yfh1 function and is likely to be involved in iron‐mediated protein–protein interactions.