Structural Research of Alpha-helical Pore-forming Toxins

Pore-forming toxins (PFTs) are important components of the molecular offensive and defensive machinery in many species. In eukaryotes, PFTs are primarily involved in the innate immune response, whilst in prokaryotes, they constitute the major virulence factor group of many pathogenic bacteria. By puncturing holes in the membrane, pathogenic PFTs can disrupt the osmotic balance of host target cells or insert secondary intracellular toxins through the pores formed in the membrane. Many pathogenic bacteria, including strains that are highly resistant to antibiotics, use PFTs in their invasive arsenal. This makes them attractive targets for developing therapies to reduce the acquired resistance that occurs with conventional antimicrobial therapy.

PFTs are produced in a soluble, often monomeric form and recognize target cells by binding to specific receptors, thereby concentrating the protein to the membrane surface prior to exposure of transmembrane hydrophobic regions, oligomerization, and membrane insertion. Depending on the secondary structure of the membrane assembly, PFTs can be classified into α-PFTs, which use amphipathic helical loops to construct the pore, or β-PFTs, in which the β-barrel is employed to traverse the membrane.

Figure 1. Structure of soluble and pore form SmhB. (Churchill-Angus A M, et al., 2021)

Table 1. Structural Research of Alpha-helical Pore-forming Toxins.

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