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Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol
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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030972/ https://www.ncbi.nlm.nih.gov/pubmed/24970201 http://dx.doi.org/10.3390/biom3040997 |
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author | Teter, Ken |
author_facet | Teter, Ken |
author_sort | Teter, Ken |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4030972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-40309722014-06-24 Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol Teter, Ken Biomolecules Review 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. MDPI 2013-12-10 /pmc/articles/PMC4030972/ /pubmed/24970201 http://dx.doi.org/10.3390/biom3040997 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Teter, Ken Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol |
title | Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol |
title_full | Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol |
title_fullStr | Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol |
title_full_unstemmed | Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol |
title_short | Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol |
title_sort | toxin instability and its role in toxin translocation from the endoplasmic reticulum to the cytosol |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030972/ https://www.ncbi.nlm.nih.gov/pubmed/24970201 http://dx.doi.org/10.3390/biom3040997 |
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