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

Item Type:Article
Title:Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex
Creators Name:Bao, G. and Clifton, M. and Hoette, T.M. and Mori, K. and Deng, S.X. and Qiu, A. and Viltard, M. and Williams, D. and Paragas, N. and Leete, T. and Kulkarni, R. and Li, X. and Lee, B. and Kalandadze, A. and Ratner, A.J. and Pizarro, J.C. and Schmidt-Ott, K.M. and Landry, D.W. and Raymond, K.N. and 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
Publisher:Nature Publishing Group
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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