Mechanism of activation of the human cysteine desulfurase complex by frataxin

Significance In humans, essential iron-sulfur (Fe-S) cluster cofactors are synthesized using an assembly complex that depends on the protein frataxin (FXN). The physiological function of FXN, which is linked to the fatal neurodegenerative disease Friedreich’s ataxia (FRDA), is still under debate. Here, we show that FXN accelerates Fe-S cluster formation by positioning a mobile loop cysteine of the assembly complex to interact with the substrate...