Solution structure of the NEAT (NEAr Transporter) domain from IsdH/HarA:: The human hemoglobin receptor in Staphylococcus aureus
Solution structure of the NEAT (NEAr Transporter) domain from IsdH/HarA:: The human hemoglobin receptor in Staphylococcus aureus
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DOI：
10.1016/j.jmb.2006.05.019
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发表时间：
2006-07-07
影响因子：
5.6
通讯作者：
Clubb, Robert T.
中科院分区：
文献类型：
--
作者：
Pilpa, Rosemarie M.;Fadeev, Evgeny A.;Clubb, Robert T.
在感染过程中，病原体金黄色葡萄球菌使用铁调节表面决定簇（Isd）蛋白从其宿主获得必需的营养铁，所述铁调节表面决定簇（Isd）蛋白从宿主血红素蛋白（hemoproteins）结合铁。四种Isd蛋白在细胞壁中展示，在那里它们作为宿主蛋白和血红素的受体发挥作用。每个受体都含有一个或多个最近发现的称为NEAT（NEAr转运蛋白）的结构域的拷贝，该结构域已被证明介导蛋白质结合。在这里，我们报告的三维溶液结构的NEAT结构域的lsdH/HarA蛋白，这是血红蛋白受体的ISD系统。这是NEAT结构域的第一个结构，揭示了它们采用由两个五链反平行β折叠组成的β三明治折叠。虽然在一级序列水平上不相关，但我们的结果表明NEAT结构域属于免疫球蛋白超家族。结合研究表明，两个lsdH/HarA NEAT结构域结合一个高铁血红蛋白分子，而来自S.金黄色葡萄球菌IsdC蛋白仅结合血红素。根据新结构比较它们的一级序列，用于预测NEAT结构域上的血红蛋白和血红素结合表面。(c)2006爱思唯尔有限公司保留所有权利。
During infections the pathogen Staphylococcus aureus procures the essential nutrient iron from its host using iron-regulated surface determinant (Isd) proteins, which scavenge heme bound iron from host hemoproteins. Four Isd proteins are displayed in the cell wall, where they function as receptors for host proteins and heme. Each of the receptors contains one or more copies of a recently discovered domain called NEAT (NEAr Transporter) that has been shown to mediate protein binding. Here we report the three-dimensional solution structure of the NEAT domain from the lsdH/HarA protein, which is the hemoglobin receptor in the Isd system. This is the first structure of a NEAT domain and reveals that they adopt a beta sandwich fold that consists of two five-stranded antiparallel beta sheets. Although unrelated at the primary sequence level, our results indicate that NEAT domains belong to the immunoglobulin superfamily. Binding studies indicate that two lsdH/HarA NEAT domains bind a single molecule of methemoglobin, while the distantly related NEAT domain from the S. aureus IsdC protein binds only heme. A comparison of their primary sequences in light of the new structure is used to predict the hemoglobin and heme binding surfaces on NEAT domains. (c) 2006 Elsevier Ltd. All rialits reserved.