Journal:IUCrJ:S2052252519002926

Determination of the Molecular Basis for Coprogen Import by Gram Negative Bacteria

Rhys Grinter and Trevor Lithgow ^[1]

Molecular Tour
Iron is an essential element for life. However, it is highly insoluble in the presence of oxygen and is therefore a scarce nutrient. In order to obtain iron, microorganisms secrete molecules into the environment that bind iron very tightly in a water-soluble form. These molecules named siderophores (Greek for iron carrier) are then re-imported in complex with iron into the cell of the producing microbe, providing the iron required for growth. Most microorganisms produce their own siderophores to scavenge iron. These siderophores are recognised and transported into the cell of the producing organism via a specific membrane protein transporter. In addition, many microorganisms produce transporter proteins for siderophores only produced by other microbes. These transporters allow the producing organism to engage in iron piracy, stealing the siderophores of other species to satisfy their iron requirements. FhuE the transporter protein that is the subject of this study is produced by bacteria and targets the fungally produced siderophore Coprogen for import. Thus, FhuE allows the bacteria to engage in iron piracy from fungal competitors in its microbial community. In this work Grinter and Lithgow have solved the crystal structure of FhuE in complex with coprogen and have shown that the binding site of this transporter has evolved to specifically recognise Coprogen in preference for other related siderophores. This specificity allows for highly effective import of Coprogen. In addition, it stops FhuE from becoming a target for siderophore mimicking antibiotics that seek to enter the bacterial cell through a Trojan horse mechanism.

An overall image of FhuE showing the trans-membrane beta barrel and the extracellular loops. Structure of FhuE, colored as a Jones’ rainbow from N-terminus (blue) to C-terminus (red).

An isometric view of FhuE (blue cartoon) showing Fe-coprogren in the substrate binding site (red-stick).

A zoomed in view of the binding pocket of FhuE containing Fe-coprogen with residues interacting with Fe-coprogen shown as blue ball-and-sticks (with surface)

A zoomed in view of the binding pocket of FhuE containing Fe-coprogen with residues interacting with Fe-coprogen shown as blue ball-and-sticks (No surface).

Fe coordination site.

Interactions between Fe-coprogen and FhuE.

PDB reference: FhuE in complex with its substrate coprogen, 6e4v.

References

1. ↑ Grinter R, Lithgow T. Determination of the molecular basis for coprogen import by Gram-negative bacteria. IUCrJ. 2019 Apr 5;6(Pt 3):401-411. doi: 10.1107/S2052252519002926. eCollection, 2019 May 1. PMID:31098021 doi:http://dx.doi.org/10.1107/S2052252519002926