FhuA: Ferrichrome-Iron Receptor

*Note: It is recomended that this tutorial be completed in order from top to bottom because some animations rely upon the previous animation's completion.

Click here to reset FhuA.

This is the FhuA molecule of E. coli . It is an integral membrane protein that acts as a ferrichrome-iron receptor. To learn more about this protein's function, please visit my FhuA website here.

On the left ( ) is a single lipopolysaccharide molecule, LPS, that is noncovalently associated with the membrane of FhuA that is located within the outer membrane of E. coli.. This LPS molecule has little to do with the actual functionality of FhuA, so we will disregard it from here on out.

This is the secondary structure of FhuA . Let us take a quick tour of the protein . FhuA consists of two main regions: an external region called the barrel region (shown in yellow), and the cork region (shown in green).

The internal cork region acts as an obstruction to prevent unwanted objects from entering the cell . Even though FhuA is a channel protein, it does require some energy to open the cork region enough to allow ferrichrome iron to pass through. It derrives thi energy from a TonB box located within the cytoplasmic membrane of E. coli.

The ferrichrome-iron molecule ( ) binds to FhuA within the protein (ferrichrome iron is shown in red).

There are several loop domains in the extracellular region of FhuA. Loop L3 ( shown in magenta) has been determined to be an essential region for ferrichrome binding. Loop L4 ( shown in orange), however, has been determined not to be essential for the actual binding of ferrichrome-iron, but it is necessary for guiding the ligand to its binding site.

Now let us take a closer look at the binding sites of ferrchrome-iron to FhuA . It binds to three residues within FhuA: Tyr 116 ( ), Arg 81 ( ), and Gln 100 ( ).

When ferrichrome-iron binds to FhuA, it causes certain allosteric changes in the protein structure, which eventually lead to the activation of the channel.

(The following images have the barrel region removed so that you can clearly see the cork domain).

One alteration occurs in a region of FhuA called apex B (shown in magenta). Upon binding, apex B moves approximately 1.8 Angstroms toward the ligand.

The movement of apex B forces a helix, dubbed the "switch" helix (shown in pink), to unwind completely. This movement causes a chain reaction which forces the remainder of the cork domain to shift.

Ultimately, the periplasmic terminus of FhuA ( shown in red), which contains a glutamic acid residue, reacts with the Ton complex located in the periplasmic space; thus allowing FhuA to obtain sufficient energy to allow the ferrichrome-iron molecule to pass through.

Click here to reset the FhuA CHIME image .

References

Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte, Wolfram. 1998. Siderophore-Mediated Iron Transport: Crystal Structure of FhuA with Bound Lipopolysaccharide. Science . 282: 2215-2220.

Locher KP, Rees B, Koebnik R, Mitschler A, Moulinier L, Rosenbusch JP, Moras D. 1998. Transmembrane Signaling across the Ligand-Gated FhuA Receptor: Crystal Structures of Free and Ferrichrome-Bound States Reveal Allosteric Changes. Cell. 95: 771-778.