title: The unfolding story of anthrax toxin translocation.
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 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.
authors: Departments of Chemistry, University of California, Berkeley, CA 94720, USA.
authors: Katie L
authors: KL
authors: Thoren
authors: Bryan A
authors: BA
authors: Krantz
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D017510:Protein Folding; D055503:Protein Multimerization; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D021122:Protein Subunits; C030325:anthrax toxin