The complex of ferric-enterobactin with its transporter from Pseudomonas aeruginosa suggests a two-site model

• Published in: Nature communications 2019-08, Vol.10 (1), p.3673-14, Article 3673
• Main Authors: Moynié, Lucile, Milenkovic, Stefan, Mislin, Gaëtan L. A., Gasser, Véronique, Malloci, Giuliano, Baco, Etienne, McCaughan, Rory P., Page, Malcolm G. P., Schalk, Isabelle J., Ceccarelli, Matteo, Naismith, James H.
• Format: Article
• Language: English
• Subjects: 13; 631/326/41/2536; 631/45; 631/535/1266; 64; 82/58; 82/80; Bacteria; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Bacterial Proteins; Bacteriology; Binding Sites; Biochemistry, Molecular Biology; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Coordination compounds; Crystallization; Crystallography, X-Ray; Enterobactin; Enterobactin - chemistry; Enterobactin - metabolism; Escherichia coli; Humanities and Social Sciences; Hydrogen bonding; Hydrogen bonds; In Vitro Techniques; Iron; Iron - metabolism; Iron Radioisotopes; Life Sciences; Membrane Proteins; Microbiology and Parasitology; multidisciplinary; Periplasm; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas aeruginosa - metabolism; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Siderophores; Siderophores - chemistry; Siderophores - metabolism; Structural Biology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11508-y

Bacteria use small molecules called siderophores to scavenge iron. Siderophore-Fe 3+ complexes are recognised by outer-membrane transporters and imported into the periplasm in a process dependent on the inner-membrane protein TonB. The siderophore enterobactin is secreted by members of the family Enterobacteriaceae, but many other bacteria including Pseudomonas species can use it. Here, we show that the Pseudomonas transporter PfeA recognises enterobactin using extracellular loops distant from the pore. The relevance of this site is supported by in vivo and in vitro analyses. We suggest there is a second binding site deeper inside the structure and propose that correlated changes in hydrogen bonds link binding-induced structural re-arrangements to the structural adjustment of the periplasmic TonB-binding motif. Bacteria produce small iron-binding molecules called siderophores, which are recognised by outer-membrane transporters. Here, the authors show that a Pseudomonas transporter recognises the siderophore enterobactin using extracellular loops distant from the pore, and propose that there is a second binding site deeper inside the structure.