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Title:
Pore-forming toxins: ancient, but never really out of fashion | Nature Reviews Microbiology
Description:
Pore-forming toxins (PFTs) are produced as virulence factors by many pathogenic bacteria. In this Review, Dal Peraro and van der Goot describe new mechanistic insights into the assembly of these toxins and their target specificity, and discuss recent therapeutic developments. Pore-forming toxins (PFTs) are virulence factors produced by many pathogenic bacteria and have long fascinated structural biologists, microbiologists and immunologists. Interestingly, pore-forming proteins with remarkably similar structures to PFTs are found in vertebrates and constitute part of their immune system. Recently, structural studies of several PFTs have provided important mechanistic insights into the metamorphosis of PFTs from soluble inactive monomers to cytolytic transmembrane assemblies. In this Review, we discuss the diverse pore architectures and membrane insertion mechanisms that have been revealed by these studies, and we consider how these features contribute to binding specificity for different membrane targets. Finally, we explore the potential of these structural insights to enable the development of novel therapeutic strategies that would prevent both the establishment of bacterial resistance and an excessive immune response.
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headline:Pore-forming toxins: ancient, but never really out of fashion
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Pore-forming toxins (PFTs) are produced as virulence factors by many pathogenic bacteria. In this Review, Dal Peraro and van der Goot describe new mechanistic insights into the assembly of these toxins and their target specificity, and discuss recent therapeutic developments. Pore-forming toxins (PFTs) are virulence factors produced by many pathogenic bacteria and have long fascinated structural biologists, microbiologists and immunologists. Interestingly, pore-forming proteins with remarkably similar structures to PFTs are found in vertebrates and constitute part of their immune system. Recently, structural studies of several PFTs have provided important mechanistic insights into the metamorphosis of PFTs from soluble inactive monomers to cytolytic transmembrane assemblies. In this Review, we discuss the diverse pore architectures and membrane insertion mechanisms that have been revealed by these studies, and we consider how these features contribute to binding specificity for different membrane targets. Finally, we explore the potential of these structural insights to enable the development of novel therapeutic strategies that would prevent both the establishment of bacterial resistance and an excessive immune response.
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