The unfolding story of anthrax toxin translocation
Article first published online: 28 MAR 2011
© 2011 Blackwell Publishing Ltd
Volume 80, Issue 3, pages 588–595, May 2011
How to Cite
Thoren, K. L. and Krantz, B. A. (2011), The unfolding story of anthrax toxin translocation. Molecular Microbiology, 80: 588–595. doi: 10.1111/j.1365-2958.2011.07614.x
- Issue published online: 20 APR 2011
- Article first published online: 28 MAR 2011
- Accepted 24 February, 2011.
The essential cellular functions of secretion and protein degradation require a molecular machine to unfold and translocate proteins either across a membrane or into a proteolytic complex. Protein translocation is also critical for microbial pathogenesis, namely bacteria can use translocase channels to deliver toxic proteins into a target cell. Anthrax toxin (Atx), a key virulence factor secreted by Bacillus anthracis, provides a robust biophysical model to characterize transmembrane protein translocation. Atx is comprised of three proteins: the translocase component, protective antigen (PA) and two enzyme components, lethal factor (LF) and oedema factor (OF). Atx forms an active holotoxin complex containing a ring-shaped PA oligomer bound to multiple copies of LF and OF. These complexes are endocytosed into mammalian host cells, where PA forms a protein-conducting translocase channel. The proton motive force unfolds and translocates LF and OF through the channel. Recent structure and function studies have shown that LF unfolds during translocation in a force-dependent manner via a series of metastable intermediates. Polypeptide-binding clamps located throughout the PA channel catalyse substrate unfolding and translocation by stabilizing unfolding intermediates through the formation of a series of interactions with various chemical groups and α-helical structure presented by the unfolding polypeptide during translocation.