Characterization of iron binding in IscA, an ancient iron-sulphur cluster assembly protein.

Iron-sulphur clusters are one of the most common types of redox centre in biology. At least six proteins (IscS, IscU, IscA, HscB, HscA and ferredoxin) have been identified as being essential for the biogenesis of iron-sulphur proteins in bacteria. It has been shown that IscS is a cysteine desulphurase that provides sulphur for iron-sulphur clusters, and that IscU is a scaffold for the IscS-mediated assembly of iron-sulphur clusters. The iron donor for iron-sulphur clusters, however, remains elusive. Here we show that IscA is an iron binding protein with an apparent iron association constant of 3.0x10(19) M(-1), and that iron-loaded IscA can provide iron for the assembly of transient iron-sulphur clusters in IscU in the presence of IscS and L-cysteine in vitro. The results suggest that IscA is capable of recruiting intracellular iron and delivering iron for iron-sulphur clusters in proteins.