the 'stalk' of the mushroom penetrates the cell membrane, rendering it permeable (see later). The 'stalk' is composed of a 14-strand β-barrel, with two strands donated from each monomer. A structure of the Vibrio cholerae cytolysin PDB:3O44 in the pore form is also heptameric; however, Staphylococcus aureus gamma-hemolysin (PDB:3B07) reveals an octomeric pore, consequently with a 16-strand 'stalk'. The Panton-Valentine leucocidin S structure (PDB: 1T5R) shows a highly related structure, but in its soluble monomeric state. This shows that the strands involved in forming the 'stalk' are in a very different conformation – shown in Fig 2. While the Bin toxin of Lysinibacillus sphaericus is able to form pores in artificial membranes and mosquito cells in culture, it also causes a series of other cellular changes including the uptake of toxin in recycling endosomes and the production of large, autophagic vesicles and the ultimate cause of cell death may be apoptotic. Similar effects on cell biology are also seen with other Toxin_10 activities but the roles of these events in toxicity remain to be established. Assembly The transition between soluble monomer and membrane-associated protomer to oligomer is not a trivial one: It is believed that β-PFTs, follow as similar assembly pathway as the CDCs (see Cholesterol-dependent cytolysins later), in that they must first assemble on the cell-surface (in a receptor-mediated fashion in some cases) in a pre-pore state. Following this, the large-scale conformational change occurs in which the membrane spanning section is formed and inserted into the membrane. The portion entering the membrane, referred to as the head, is usually apolar and hydrophobic, this produces an energetically favorable insertion of the pore-forming toxin. Specificity Some β-PFTs such as clostridial ε-toxin and Clostridium perfringens enterotoxin (CPE) bind to the cell membrane via specific receptors – possibly certain claudins for CPE, possibly GPI anchors or other sugars for ε-toxin – these receptors help raise the local concentration of the toxins, allowing oligomerisation and pore formation. The BinB Toxin_10 component of the Lysinibacillus sphaericus Bin toxin specifically recognises a GPI anchored alpha glycosidase in the midgut of Culex and Anopheles mosquitoes but not the related protein found in Aedes mosquitoes, hence conferring specificity on the toxin. The cyto-lethal effects of the pore When the pore is formed, the tight regulation of what can and cannot enter/leave a cell is disrupted. Ions and small molecules, such as amino acids and nucleotides within the cell,