Identification of the cellular receptor for anthrax toxin
Identification of the cellular receptor for anthrax toxin
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DOI：
10.1038/n35101999
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发表时间：
2001-11-08
期刊：
影响因子：
64.8
通讯作者：
Young, JAT
中科院分区：
文献类型：
--
作者：
Bradley, KA;Mogridge, J;Young, JAT
炭疽杆菌是炭疽的病原体，它分泌的三毒可以帮助细菌逃避免疫系统，并在全身感染时杀死宿主。该毒素的两种成分通过酶修饰哺乳动物细胞胞浆内的底物：水肿因子（of）是一种腺苷酸环化酶，通过多种机制损害宿主防御，包括抑制吞噬（1,2）；致死因子（lethal factor， LF）是一种锌依赖性蛋白酶，可切割丝裂原活化的蛋白激酶激酶并导致巨噬细胞的裂解（3-5）。保护性抗原（PA）是第三种组分，与细胞受体结合并介导酶组分向细胞质溶胶的传递。在这里，我们描述克隆人类PA受体使用遗传互补的方法。这种受体被称为ATR（炭疽毒素受体），是一种I型膜蛋白，具有细胞外血管性血液病因子a结构域，直接与PA结合。此外，该结构域的可溶性版本可以保护细胞免受毒素的作用。
The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis(1,2); lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages(3-5). Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.