Journal
PROTEIN SCIENCE
Volume 21, Issue 1, Pages 1-12Publisher
WILEY
DOI: 10.1002/pro.752
Keywords
anthrax; toxin; protective antigen; pore; pH; membrane protein; review
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Funding
- NIH-COBRE [P20 RR017708-06]
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The protective antigen is a key component of the anthrax toxin, as it allows entry of the enzymatic components edema factor and lethal factor into the host cell, through the formation of a membrane spanning pore. This event is absolutely critical for the pathogenesis of anthrax, and although we have yet to understand the mechanism of pore formation, recent developments have provided key insights into how this process may occur. Based on the available data, a model is proposed for the kinetic steps for protective antigen conversion from prepore to pore. In this model, the driving force for pore formation is the formation of the phi (?)-clamp, a region that forms a leak-free seal around the translocating polypeptide. Formation of the ?-clamp elicits movements within the prepore that provide steric freedom for the subsequent conformational changes required to form the membrane spanning pore.
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