Iron Is a Physiological Ligand of SecA-like Metal Binding Domains

The ATPase SecA is required for translocation of most proteins across the cytoplasmic membrane in bacteria. In Escherichia coli, SecA contains a small metal binding domain (MBD) at its extreme C-terminus that is widely conserved in other bacterial species and is required for its interaction with SecB. The MBD is thought to coordinate Zn2+ via a conserved cysteine-containing motif. Here, we investigated the metal binding properties of two E. coli proteins that contain SecA-like MBDs: YecA and YchJ. Both proteins copurify with metal, predominantly zinc. However, both proteins also copurify with significant amounts of iron. In YecA, iron binding is mediated by the MBD. Re-evaluation of the metal-binding properties of SecA indicate that: (i) SecA copurifies with stoichiometric amounts of iron; (ii) binding is mediated by the MBD; (iii) the MBD binds to iron with equal or greater affinity than to zinc; and (iv) the affinity for iron (but not for zinc) is mediated by a highly conserved serine in the metal-binding motif. Taken together, our results suggest that iron is a physiological ligand of SecA-like MBDs.