Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
Sumario: | 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. |
---|