TCBG Seminar

How Anthrax Toxins Enter a Host Cell: A Molecular Dynamics Study

Dr. Mu Gao
Theoretical and Computational Biophysics Group
University of Illinois
Urbana, Illinois

Monday, April 17, 2006
3:00 pm (CT)
3269 Beckman Institute


Bacillus anthracis, the cause of anthrax, is one of the most lethal bacteria. The bacterium attacks the cells of the host's immune system, the so-called macrophages, as well as many tissue cells. 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. To invade a host cell, the toxins take an intricate entry route that involves binding to a cell receptor and inducing the cell to internalize the toxins in a bubble like endosome. The bubble membrane wall is then punctured by protective antigens forming a channel upon an acidifying trigger from the host, and finally the lethal factors and edema factors slip into the cell through the pore. Molecular dynamics simulations of an anthrax toxin- receptor complex reveal how acidic conditions in the endosome trigger conformational changes of the PA complex necessary for pore formation, and provide structural insights into the role of unusual interactions between the protective antigens and its cellular receptors.

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