Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol
AbstractAB 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–toxin interactions involved with A chain unfolding in the ER and A chain refolding in the cytosol.
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Teter, K. Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol. Biomolecules 2013, 3, 997-1029.
Teter K. Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol. Biomolecules. 2013; 3(4):997-1029.Chicago/Turabian Style
Teter, Ken. 2013. "Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol." Biomolecules 3, no. 4: 997-1029.