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The unfolding story of anthrax toxin translocation
Author(s) -
Thoren Katie L.,
Krantz Bryan A.
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2011.07614.x
Subject(s) - anthrax toxin , translocase , biology , bacillus anthracis , transmembrane protein , chromosomal translocation , virulence factor , microbiology and biotechnology , cytosol , transport protein , secretion , biophysics , biochemistry , toxin , virulence , fusion protein , bacteria , receptor , enzyme , genetics , gene , recombinant dna
Summary 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.