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9.A.8 The Ferrous Iron Uptake (FeoB) Family

The FeoB protein of E. coli is an integral membrane protein of 773 amino acyl residues which is predicted to span the membrane 8-13 times as α-helices. It has been implicated in Fe²⁺ uptake (Kammler et al., 1993). Homologous proteins are encoded within the genomes of the many bacteria and archaea. The protein possesses an N-terminal 300 amino acyl residue hydrophilic domain that bears at its N-terminus an ATP/GTP binding motif. This N-terminal hydrophilic domain is homologous to prokaryotic and eukaryotic GTP binding proteins including the E. coli Era protein (P06616). The protein has therefore been postulated to be energized by ATP or GTP hydrolysis. GTP binding has been shown to be required for efficient Fe²⁺ uptake, but GTP is hydrolyzd very slowly (Marlovits et al., 2002). Nevertheless, GTP hydrolysis is essential for Fe²⁺ transport (Hantke, 2003). Whether FeoB is directly or indirectly involved in Fe²⁺ uptake is not entirely clear (Hantke, 2003). Consequently, FeoB is proposed to be regulated by the intramolecular G-protein-like domain.

A FeoB homologue is present in Helicobacter pylori. This system takes up Fe²⁺ with high affinity (0.5 μM) in a process that is inhibited by FCCP, DCCD and vanadate, indicating that uptake is energized by ATP hydrolysis (Velayudhan et al., 2000). Fe³⁺ is first converted to Fe²⁺ by an extracytoplasmic Fe³⁺ reductase, and the resultant Fe²⁺ is taken up by FeoB. FeoB appears to provide the major pathway for Fe²⁺ uptake in H. pylori, and it is essential for colonization of the murine gastric mucosa. A similar FeoB homologue in the spirochete Leptospira biflexa has been implicated in Fe²⁺ uptake (Louvel et al., 2005).

Prokaryotic FeoB proteins are involved in G protein coupled Fe²⁺ transport. They are unique in that the G protein is directly tethered to the membrane domain. Guilfoyle et al., 2009 reported the structure of the soluble domain of FeoB, including the G protein domain, and its assembly into an unexpected trimer. Comparisons between nucleotide free and liganded structures reveal the closed and open state of a central cytoplasmic pore, respectively. In addition, these data provide the first observation of a conformational switch in the nucleotide-binding G5 motif, defining the structural basis for GDP release. From these results, structural parallels are drawn to eukaryotic G protein coupled membrane processes (Guilfoyle et al., 2009).

The generalized transport reaction catalyzed by FeoB is presumably:

Fe²⁺ (out) + energy → (out) + Fe²⁺ (in).