FepA enterobactin receptor

As mentioned above, transport of siderophores across the cytoplasmic membrane is less specific than the translocation through the outer membrane. In E. coli three different outer membrane proteins (among them FepA the receptor for enterobactin produced by most E. coli strains) recognise siderophores of the catechol type (enterobactin and structurally related compounds), while only one ABC system is needed for the passage into the cytosol. Likewise, OM receptors FhuA, FhuE, and Iut are needed to transport a number of different ferric hydroxamates, whereas the FhuBCD proteins accept a variety of hydroxamate type ligands such as albomycin, ferrichrome, coprogen, aerobactin, shizokinen, rhodotorulic acid, and ferrioxamine B [165,171], For the vast majority of systems, the substrate specificity has not been elucidated, but it can be assumed that many siderophore ABC permeases might be able to transport several different but structurally related substrates. 

The largest /f-bar re Is have been observed with the monomeric iron transporter proteins FhuA and FepA. The structure of FhuA was established independently by two groups (Locher et al., 1998 Ferguson et al., 1998). It is known with and without a ligated siderophore. The structure of the ferric enterobactin receptor FepA is homologous to that of FhuA showing identical topology and a similar transport mechanism (Buchanan etal., 1999). In both cases there are more than 700 residues assembled in two domains an N-terminal 150-residue domain is located inside a C-terminal 22-stranded (6-barrel with a shear number S = 24. 

Figure 10 A schematic drawing of the cell envelope of E. coli consisting of the cytoplasmic membrane, the periplasm, and the outer membrane. Various proteins are shown, sets of which represent specific siderophore-transport systems. Outer-membrane receptors (OMR) shown here are FepA (enterobactin), lutA (aerobactin), Fee A (Fe dicitrate), FhuA (ferrichrome), and FhuE (coprogen, Fe rhodotorulate, and ferrioxamine B). FoxA (ferrioxamine B), is not a receptor of E.coli, but of the closely related Salmonella. Not shown here are the receptors Fiu and Cir (Fe (DHBS) n indicates 3 possible linear degradation products of enterobactin) and FeO, a transport system for Fe . Details are discussed in Section 5.1...

Klug CS, Eaton SS, Eaton GR, Feix JB. 1998. Ligand-induced conformational change in the ferric enterobactin receptor FepA as studied by site-directed spin labeling and time-domain ESR. Biochemistry 37(25) 9016-9023. 

The FhuA receptor of E. coli transports the hydroxamate-type siderophore ferrichrome (see Figure 9), the structural similar antibiotic albomycin and the antibiotic rifamycin CGP 4832. Likewise, FepA is the receptor for the catechol-type siderophore enterobactin. As monomeric proteins, both receptors consist of a hollow, elliptical-shaped, channel-like 22-stranded, antiparallel (3-barrel, which is formed by the large C-terminal domain. A number of strands extend far beyond the lipid bilayer into the extracellular space. The strands are connected sequentially using short turns on the periplasmic side, and long loops on the extracellular side of the barrel. 

The receptor for Fem-enterobactin retains its affinity for the complex and for colicin B in vitro after extraction. The receptor has a dissociation constant of about 10 nmol dm-3 for Fem-enterobactin. The gene for synthesis of the receptor is FepA... 

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