Pilpa Rosemarie M, Fadeev Evgeny A, Villareal Valerie A, Wong Melissa L, Phillips Martin, Clubb Robert T
Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, and the Molecular Biology Institute, University of California-Los Angeles, 611 Charles E. Young Drive, Los Angeles, CA 90095-1570, USA.
J Mol Biol. 2006 Jul 7;360(2):435-47. doi: 10.1016/j.jmb.2006.05.019. Epub 2006 May 22.
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 IsdH/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 IsdH/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.
在感染过程中，病原菌金黄色葡萄球菌利用铁调节表面决定簇（Isd）蛋白从宿主获取必需营养物质铁，这些蛋白从宿主血红蛋白中清除血红素结合铁。四种Isd蛋白展示在细胞壁上，在那里它们作为宿主蛋白和血红素的受体发挥作用。每个受体包含一个或多个最近发现的名为NEAT（近转运体）的结构域拷贝，该结构域已被证明可介导蛋白质结合。在此，我们报道了来自IsdH/HarA蛋白的NEAT结构域的三维溶液结构，IsdH/HarA蛋白是Isd系统中的血红蛋白受体。这是NEAT结构域的首个结构，揭示了它们采用由两个五链反平行β折叠片组成的β折叠夹心结构。尽管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IsdH/HarA NEAT结构域结合单个高铁血红蛋白分子，而来自金黄色葡萄球菌IsdC蛋白的远亲NEAT结构域仅结合血红素。根据新结构对它们的一级序列进行比较，以预测NEAT结构域上的血红蛋白和血红素结合表面。
