(IscS‐IscU)₂ Complex Structures Provide Insights into Fe₂S₂ Biogenesis and Transfer

Abstract

The center of attention: IscS cysteine desulfurases and IscU scaffolds are involved in biological iron–sulfur cluster assembly. The X‐ray structure of an anaerobically produced, mutated (Fe2S2‐(IscS‐IscUD35A))2 complex reveals a cluster coordinated by three IscU cysteines and the IscS active cysteine (see picture). In air‐exposed crystals the cluster is oxidized to an Fe2S–S center; D35 is essential for complex dissociation.

The Sulfur Carrier Protein TusA Has a Pleiotropic Role in Escherichia coli That Also Affects Molybdenum Cofactor Biosynthesis*

“…Consistent with this hypothesis are studies by Marinoni et al (42), who solved the crystal structure of the IscS-IscU complex from Archaeoglobus fulgidus. In the crystal structure the participation of the catalytic IscS-Cys321 as a transient ligand in the formation of the 2Fe2S cluster on IscU was resolved (42). Thus, during FeS cluster formation, a portion of IscS would not be available for acceptor proteins like TusA or ThiI.…”

X-ray snapshots of possible intermediates in the time course of synthesis and degradation of protein-bound Fe 4 S 4 clusters

“…This result favors in turn a concerted mechanism for Fe-S cluster assembly by ISC, where two ferrous ions bind simultaneously the first persulfide S 0 from the active Cys residue of IscS at the assembly site of IscU and reduce it to S 2− . We have already suggested such mechanism based on the Archeoglobus fulgidus (IscS-IscU) 2 complex structure (27).…”

Architecture of the Yeast Mitochondrial Iron-Sulfur Cluster Assembly Machinery

“…Two Isu1 subunits, one from each [Yfh1] 3 ⅐[Isu1] 3 sub-complex, face each other with their respective [2Fe-2S] coordinating sites formed by the invariant Cys-69, Cys-96, Cys-139, and His-138 residues, known to be involved in Fe-S cluster coordination (Fig. 9A) (15,33,34). In each site, these residues are within ϳ2-4 Å from each other, in a manner that appears suitable to coordinate one [2Fe-2S] cluster (Fig.…”

“…The crystal structure of an Escherichia coli [IscS]⅐[IscU] complex (PDB 3 code 3LVL) showed an elongated heterodimer consisting of one IscS and one IscU subunit (14), and furthermore the crystal structure of an Archaeoglobus fulgidus [IscS] 2 ⅐[IscU] 2 complex (PDB code 4EB5) showed an elongated heterotetramer consisting of two IscS and two IscU subunits (15). Additional studies demonstrated similar bacterial and yeast heterotetramers in which a dimer of IscS/ Nfs1 binds to one IscU/Isu1 monomer at each end, and it was further proposed that one CyaY/Yfh1 monomer could bind in a pocket between the cysteine desulfurase and the scaffold (10, 16 -18).…”