Binding of anthrax toxin to its receptor is similar to α integrin-ligand interactions
Binding of anthrax toxin to its receptor is similar to α integrin-ligand interactions
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DOI：
10.1074/jbc.m307900200
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发表时间：
2003-12-05
影响因子：
4.8
通讯作者：
Young, JAT
中科院分区：
文献类型：
--
作者：
Bradley, KA;Mogridge, J;Young, JAT
炭疽芽孢杆菌产生的分泌蛋白毒素有助于这种病原体的毒力，并可导致炭疽感染期间出现的许多症状，包括休克和猝死。炭疽毒素的细胞结合成分是保护性抗原，通过首先与细胞炭疽毒素受体ATR的细胞外整合素样插入(I)结构域直接结合来介导毒素进入细胞。在这里，我们报告了这种相互作用需要在受体中有一个完整的金属离子依赖的黏附位点(MIDAS)以及特定的二价阳离子的存在。此外，我们还证明了毒素-受体的相互作用严重依赖于保护性抗原的天冬氨酸-683羧基，它从受体结合表面投射出来。我们认为这个羧基完成了ATR的MIDAS金属的配位，模拟了整合素与配体的相互作用。
The secreted protein toxin produced by Bacillus anthracis contributes to virulence of this pathogen and can cause many of the symptoms seen during an anthrax infection, including shock and sudden death. The cell-binding component of anthrax toxin, protective antigen, mediates entry of the toxin into cells by first binding directly to the extracellular integrin-like inserted ( I) domain of the cellular anthrax toxin receptor, ATR. Here we report that this interaction requires an intact metal ion-dependent adhesion site (MIDAS) in the receptor as well as the presence of specific divalent cations. Also, we demonstrate that the toxin-receptor interaction is critically dependent on the Asp-683 carboxylate group of protective antigen, which projects from the receptor binding surface. We propose that this carboxylate group completes the coordination of the MIDAS metal of ATR, mimicking integrin-ligand interactions.