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Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins

ABC toxins are pore-forming toxins characterised by the presence of three distinct components assembled into a hetero-oligomeric toxin complex ranging in size from 1.5–2.5 MDa. Most ABC toxins studied to date appear to be insecticidal toxins, although genes predicted to encode for homologous assembl...

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Autores principales: Aleksandrova, Nadezhda A., Roche, Solace G., Low, Yu Shang, Landsberg, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317148/
https://www.ncbi.nlm.nih.gov/pubmed/37199493
http://dx.doi.org/10.1042/BST20221409
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author Aleksandrova, Nadezhda A.
Roche, Solace G.
Low, Yu Shang
Landsberg, Michael J.
author_facet Aleksandrova, Nadezhda A.
Roche, Solace G.
Low, Yu Shang
Landsberg, Michael J.
author_sort Aleksandrova, Nadezhda A.
collection PubMed
description ABC toxins are pore-forming toxins characterised by the presence of three distinct components assembled into a hetero-oligomeric toxin complex ranging in size from 1.5–2.5 MDa. Most ABC toxins studied to date appear to be insecticidal toxins, although genes predicted to encode for homologous assemblies have also been found in human pathogens. In insects, they are delivered to the midgut either directly via the gastrointestinal tract, or via a nematode symbiont, where they attack the epithelial cells and rapidly trigger widespread cell death. At the molecular level, the homopentameric A subunit is responsible for binding to lipid bilayer membranes and introducing a protein translocation pore, through which a cytotoxic effector — encoded at the C-terminus of the C subunit — is delivered. The B subunit forms a protective cocoon that encapsulates the cytotoxic effector, part of which is contributed by the N-terminus of the C subunit. The latter also includes a protease motif that cleaves the cytotoxic effector, releasing it into the pore lumen. Here, we discuss and review recent studies that begin to explain how ABC toxins selectively target specific cells, establishing host tropism, and how different cytotoxic effectors trigger cell death. These findings allow for a more complete understanding of how ABC toxins function in an in vivo context, which in turn provides a stronger foundation for understanding how they cause disease in invertebrate (and potentially also vertebrate) hosts, and how they might be re-engineered for therapeutic or biotechnological purposes.
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spelling pubmed-103171482023-07-04 Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins Aleksandrova, Nadezhda A. Roche, Solace G. Low, Yu Shang Landsberg, Michael J. Biochem Soc Trans Review Articles ABC toxins are pore-forming toxins characterised by the presence of three distinct components assembled into a hetero-oligomeric toxin complex ranging in size from 1.5–2.5 MDa. Most ABC toxins studied to date appear to be insecticidal toxins, although genes predicted to encode for homologous assemblies have also been found in human pathogens. In insects, they are delivered to the midgut either directly via the gastrointestinal tract, or via a nematode symbiont, where they attack the epithelial cells and rapidly trigger widespread cell death. At the molecular level, the homopentameric A subunit is responsible for binding to lipid bilayer membranes and introducing a protein translocation pore, through which a cytotoxic effector — encoded at the C-terminus of the C subunit — is delivered. The B subunit forms a protective cocoon that encapsulates the cytotoxic effector, part of which is contributed by the N-terminus of the C subunit. The latter also includes a protease motif that cleaves the cytotoxic effector, releasing it into the pore lumen. Here, we discuss and review recent studies that begin to explain how ABC toxins selectively target specific cells, establishing host tropism, and how different cytotoxic effectors trigger cell death. These findings allow for a more complete understanding of how ABC toxins function in an in vivo context, which in turn provides a stronger foundation for understanding how they cause disease in invertebrate (and potentially also vertebrate) hosts, and how they might be re-engineered for therapeutic or biotechnological purposes. Portland Press Ltd. 2023-06-28 2023-05-18 /pmc/articles/PMC10317148/ /pubmed/37199493 http://dx.doi.org/10.1042/BST20221409 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of University of Queensland in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with CAUL.
spellingShingle Review Articles
Aleksandrova, Nadezhda A.
Roche, Solace G.
Low, Yu Shang
Landsberg, Michael J.
Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins
title Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins
title_full Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins
title_fullStr Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins
title_full_unstemmed Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins
title_short Recent insights into mechanisms of cellular toxicity and cell recognition associated with the ABC family of pore-forming toxins
title_sort recent insights into mechanisms of cellular toxicity and cell recognition associated with the abc family of pore-forming toxins
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317148/
https://www.ncbi.nlm.nih.gov/pubmed/37199493
http://dx.doi.org/10.1042/BST20221409
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