Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Biomolecules 2013, 3(4), 997-1029; doi:10.3390/biom3040997
Review

Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol

Received: 4 November 2013; in revised form: 26 November 2013 / Accepted: 27 November 2013 / Published: 10 December 2013
(This article belongs to the Special Issue Protein Folding and Misfolding)
View Full-Text   |   Download PDF [501 KB, uploaded 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 AB toxin; cholera toxin; cytolethal distending toxin; endoplasmic reticulum-associated degradation; exotoxin A; pertussis toxin; ricin toxin; Shiga toxin; toxin structure; ubiquitin-independent degradation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


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.

AMA Style

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.


Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert