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anthrax-toxin-receptor complex

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Bacillus anthracis, the cause of anthrax, is one of the most lethal bacteria. In addition to its ability to infect animal and human cells, the bacterium attacks also the cells of the host's immune system, the so-called macrophages. For this purpose the anthrax bacterium releases three types of proteins, or toxins, into the blood stream of the host: protective antigen, lethal factor, and edema factor, referred to as PA, LF, and EF, respectively. LF and EF team up with PA, which transports them into a host macrophage cell. Once inside the cell, LF converts ATP to cyclic AMP, while EF disables MAPKKs, a family of signaling proteins. These attacks disrupt various cellular signaling pathways of macrophages and some other cells, essentially shutting down the host's immune system and often leading to death of the host. To invade macrophages, the toxins take an intricate entry route that involves binding to a cell receptor, capillary morphogenesis protein 2 (CMG2), inducing the cell to internalize the toxins in a bubble like membrane (endosome), the bubble wall being then punctured by seven PAs forming a channel upon a chemical (acidifying) trigger from the host; the channel permits then their lethal cargo, LFs and EFs, to slip into the cell. How exactly the PAs punctured the endosome wall remained a mystery. In a recent report the entry route has been resolved now in greater detail through molecular dynamics simulations using NAMD. The report reveals how acidic conditions in the endosome trigger conformational changes of the PA complex necessary for pore formation, and provides structural insights into the role of unusual interactions between the PAs and its receptor CMG2. Visit also our anthrax toxin webpage.