Unique Iron Coordination in Iron-chelating Molecule Vibriobactin Helps Vibrio cholerae Evade Mammalian Siderocalin-mediated Immune Response.
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Unique Iron Coordination in Iron-chelating Molecule Vibriobactin Helps Vibrio cholerae Evade Mammalian Siderocalin-mediated Immune Response.
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Authors: Li N Zhang C Li B Liu X Huang Y Xu S Gu L
Address: From the State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100 and.
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Iron is essential for the survival of almost all bacteria. Vibrio cholerae acquires iron through the secretion of a catecholate siderophore called Vibriobactin. At present, how vibriobactin chelates ferric ion remains controversial. In addition, the mechanisms underlying the recognition of ferric vibriobactin by the siderophore transport system and its delivery into the cytoplasm specifically have not been clarified. In this study, we report the high-resolution structures of the ferric vibriobactin periplasmic binding protein ViuP and its complex with ferric vibriobactin. The holo-ViuP structure reveals that ferric vibriobactin does not adopt the same iron Coordination as that of other catecholate siderophores such as enterobactin. The three catechol moieties donate five, rather than six, oxygen atoms as iron ligands. The sixth iron ligand is provided by a nitrogen atom from the second oxazoline ring. This kind of iron coordination results in the protrusion of the second catechol moiety and renders the electrostatic surface potential of ferric vibriobactin less negatively polarized compared with ferric enterobactin. To accommodate ferric vibriobactin, ViuP has a deeper subpocket to hold the protrusion of the second catechol group. This structural characteristic has not been observed in other catecholate siderophore-binding proteins. Biochemical data show that Siderocalin, which is part of the Mammalian innate Immune system, cannot efficiently sequester ferric vibriobactin in vitro, although it can capture many catecholate siderophores with high efficiency. Our findings suggest that the Unique iron coordination found in ferric vibriobactin may be utilized by some pathogenic bacteria to Evade the siderocalin-mediated innate immune Response of mammals.
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