How the anthrax toxin gets into cells is visualized in a paper published online this week in Nature Structural & Molecular Biology. Understanding the machinery underlying such a basic process in the anthrax lifecycle allows researchers to look for weak spots to target such pathogens.
Bacillus anthracis, the bacterium that causes anthrax, produces the toxin lethal factor (LF), which, once it enters cells, leads to fatality for patients. But injecting these proteins into host cells is akin to getting a ship into a bottle, in that they have to be unfolded to get them through a narrow channel into the cell where they are refolded into their active shape.
The anthrax lethal toxin injection system itself consists of protective antigen (PA) and lethal factor (LF), with LF unfolding for translocation into the host cell. Structural and functional analyses indicate how each of four LF molecules unfolds and binds on the surface of eight PA molecules in clefts that help stabilize the unfolded state. This indicates how the bacterium can control the shape of the molecule and ensure it remains functional.