Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex.
Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex.
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DOI：
10.1038/nchembio.402
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发表时间：
2010-08
影响因子：
14.8
通讯作者：
Barasch J
中科院分区：
文献类型：
--
作者：
Bao G;Clifton M;Hoette TM;Mori K;Deng SX;Qiu A;Viltard M;Williams D;Paragas N;Leete T;Kulkarni R;Li X;Lee B;Kalandadze A;Ratner AJ;Pizarro JC;Schmidt-Ott KM;Landry DW;Raymond KN;Strong RK;Barasch J
Lipocalin是一种能结合有机小分子的分泌型蛋白质。SCN-NGAL[称为中性粒细胞明胶酶相关的Lipocalin，Siderocalin，Lipocalin 2]隔离细菌铁螯合剂，称为铁载体，从而阻止细菌的生长。然而，SCN-NGAL也在无菌疾病中显著表达，这意味着它结合了额外的配体并发挥了额外的功能。使用化学筛选、结晶学和荧光方法，我们报道了SCN-NGAL将铁与一种称为儿茶酚的小代谢产物结合在一起。该复合体的形成阻止了铁的反应性，并使其一旦进入体内循环就得以运输。然后，SCN-NGAL通过一种对pH敏感的机制回收内体中的铁。由于儿茶酚来自细菌和哺乳动物对饮食化合物的代谢，SCN-NGAL：儿茶酚：铁复合体代表了一种不可预见的微生物-宿主相互作用，它模拟了SCN-NGAL：铁载体的相互作用，但相反，它在无菌组织中运输铁。这些结果确定了一个内源性的铁载体，这可能与SCN-NGAL在不同疾病中的不同作用有关。
The lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal [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. Since catechols derive from bacterial and mammalian metabolism of dietary compounds, the Scn-Ngal:catechol:iron 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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影响因子：
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作者：
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