Mar 30, 2011

The unfolding story of anthrax toxin translocation

Molecular Microbiology
Katie L Thoren, Bryan A Krantz

Abstract

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 s...Continue Reading

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  • Citations34

Mentioned in this Paper

Anthrax protective antigen
Pathogenic Aspects
Pathogenesis
Anthrax toxin edema factor
Tang Hsi Ryu Syndrome
Bacterial Toxins
Complex (molecular entity)
Translocase
Integral to Membrane
Proteolytic Enzyme

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