The unfolding story of anthrax toxin translocation

摘要: The essential cellular functions of secretion and protein degradation require a molecular machine to unfold translocate proteins either across membrane or into proteolytic complex. Protein translocation is also critical for microbial pathogenesis, namely bacteria can use translocase channels deliver toxic target cell. Anthrax toxin (Atx), key virulence factor secreted by Bacillus anthracis, provides robust biophysical model characterize transmembrane translocation. Atx comprised three proteins: the component, protective antigen (PA) two enzyme components, lethal (LF) oedema (OF). forms an active holotoxin complex containing ring-shaped PA oligomer bound multiple copies LF OF. These complexes are endocytosed mammalian host cells, where protein-conducting channel. proton motive force unfolds translocates OF through Recent structure function studies have shown that during in force-dependent manner via series metastable intermediates. Polypeptide-binding clamps located throughout channel catalyse substrate unfolding stabilizing intermediates formation interactions with various chemical groups α-helical presented polypeptide