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Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA
Received: 4 November 2013; in revised form: 26 November 2013 / Accepted: 27 November 2013 / Published: 10 December 2013
Abstract: 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–toxin interactions involved with A chain unfolding in the ER and A chain refolding in the cytosol.
Keywords: AB toxin; cholera toxin; cytolethal distending toxin; endoplasmic reticulum-associated degradation; exotoxin A; pertussis toxin; ricin toxin; Shiga toxin; toxin structure; ubiquitin-independent degradation
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MDPI and ACS Style
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.
Teter, Ken. 2013. "Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol." Biomolecules 3, no. 4: 997-1029.