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

Nat Chem Biol. 2010 Aug;6(8):602-9. doi: 10.1038/nchembio.402.

Guanhu Bao ¹, Matthew Clifton, Trisha M Hoette, Kiyoshi Mori, Shi-Xian Deng, Andong Qiu, Melanie Viltard, David Williams, Neal Paragas, Thomas Leete, Ritwij Kulkarni, Xiangpo Li, Belinda Lee, Avtandil Kalandadze, Adam J Ratner, Juan Carlos Pizarro, Kai M Schmidt-Ott, Donald W Landry, Kenneth N Raymond, Roland K Strong, Jonathan Barasch

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Affiliation

1 College of Physicians and Surgeons of Columbia University, New York, New York, USA.

PMID: 20581821 DOI: 10.1038/nchembio.402

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.

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