Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex.

Publication Type:

Journal Article


Nature chemical biology, Volume 6, Issue 8, p.602-9 (2010)


2010, Acute-Phase Proteins, Animals, Basic Sciences Division, Catechols, Cell Line, Center-Authored Paper, Chromatography, High Pressure Liquid, Computational Biology, Crystallography, X-Ray, Endosomes, Fluorescent Dyes, Humans, Iron, Iron Chelating Agents, Kidney, Ligands, Lipocalins, MICE, Oncogene Proteins, Protein Binding, Recombinant Proteins, Siderophores


The lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal (also known as neutrophil gelatinase associated lipocalin, siderocalin, lipocalin 2) sequesters bacterial iron chelators, called siderophores, and consequently blocks bacterial growth. However, Scn-Ngal is also prominently expressed in aseptic diseases, implying that it binds additional ligands and serves additional functions. Using chemical screens, crystallography and fluorescence methods, we report that Scn-Ngal binds iron together with a small metabolic product called catechol. The formation of the complex blocked the reactivity of iron and permitted its transport once introduced into circulation in vivo. Scn-Ngal then recycled its iron in endosomes by a pH-sensitive mechanism. As catechols derive from bacterial and mammalian metabolism of dietary compounds, the Scn-Ngal-catechol-Fe(III) complex represents an unforeseen microbial-host interaction, which mimics Scn-Ngal-siderophore interactions but instead traffics iron in aseptic tissues. These results identify an endogenous siderophore, which may link the disparate roles of Scn-Ngal in different diseases.