%0 Journal Article
%T Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol
%A Ken Teter
%J Biomolecules
%D 2013
%I MDPI AG
%R 10.3390/biom3040997
%X AB toxins enter a host cell by receptor-mediated endocytosis. The catalytic A chain then crosses the endosome or endoplasmic reticulum (ER) membrane to reach its cytosolic target. Dissociation of the A chain from the cell-binding B chain occurs before or during translocation to the cytosol, and only the A chain enters the cytosol. In some cases, AB subunit dissociation is facilitated by the unique physiology and function of the ER. The A chains of these ER-translocating toxins are stable within the architecture of the AB holotoxin, but toxin disassembly results in spontaneous or assisted unfolding of the isolated A chain. This unfolding event places the A chain in a translocation-competent conformation that promotes its export to the cytosol through the quality control mechanism of ER-associated degradation. A lack of lysine residues for ubiquitin conjugation protects the exported A chain from degradation by the ubiquitin-proteasome system, and an interaction with host factors allows the cytosolic toxin to regain a folded, active state. The intrinsic instability of the toxin A chain thus influences multiple steps of the intoxication process. This review will focus on the host¨Ctoxin interactions involved with A chain unfolding in the ER and A chain refolding in the cytosol.
%K AB toxin
%K cholera toxin
%K cytolethal distending toxin
%K endoplasmic reticulum-associated degradation
%K exotoxin A
%K pertussis toxin
%K ricin toxin
%K Shiga toxin
%K toxin structure
%K ubiquitin-independent degradation
%U http://www.mdpi.com/2218-273X/3/4/997