Item Type: | Article |
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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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