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

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Item Type:	Article
Title:	Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex
Creators Name:	Bao, G., Clifton, M., Hoette, T.M., Mori, K., Deng, S.X., Qiu, A., Viltard, M., Williams, D., Paragas, N., Leete, T., Kulkarni, R., Li, X., Lee, B., Kalandadze, A., Ratner, A.J., Pizarro, J.C., Schmidt-Ott, K.M., Landry, D.W., Raymond, K.N., Strong, R.K. and Barasch, J.
Abstract:	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.
Keywords:	Acute-Phase Proteins, Catechols, Cell Line, Computational Biology , Endosomes, Fluorescent Dyes, High Pressure Liquid Chromatography, Iron, Iron Chelating Agents, Kidney, Ligands, Lipocalins, Oncogene Proteins, Protein Binding, Recombinant Proteins, Siderophores, X-Ray Crystallography, Animals, Mice
Source:	Nature Chemical Biology
ISSN:	1552-4450
Publisher:	Nature Publishing Group
Volume:	6
Number:	8
Page Range:	602-609
Date:	August 2010
Official Publication:	https://doi.org/10.1038/nchembio.402
PubMed:	View item in PubMed

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