A plus B Subunit Arrangement

Many toxins act intracellularly and consist of two components: subunit A which is responsible for the enzymatic activity of the toxin and subunit B is concerned with binding to a specific receptor on the host cell membrane and transferring the enzyme across the membrane. The enzymatic component is not active until it is released from the native (A+B) toxin. Isolated A subunits are enzymatically active but lack binding and cell entry capability. Isolated B subunits may bind to target cells (and even block the binding of the native toxin), but they are nontoxic.

Pore forming toxins:

Lipids are hydrophobic molecules which are essential constituents of membranes in the cells, whereas bacterial toxins are mainly hydrophilic proteins. All bacterial toxins interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. When bound to the receptor, some toxins act locally at the cell membrane, triggering pore formation across the lipid bilayer to release cell nutrients or kill target by disturbing their membrane. In contrast, other toxins enter cells and modify an intracellular target. These active toxins are trapped into endocytotic vesicles and follow different steps to access into the cytosol. One of the example is Staphylococcus which  secretes pore forming toxins, to alter the host cells and trigger a release of nutrients useful for their growth.

Pore forming toxins use two mechanisms to form pores in the cell membrane, according to the structural domain building the channel:

• Insertion of amphipathic α-helices or α-PFT
  Represented by colicins and staphylococcus δ-toxins
• Insertion of amphopathic β-hairpins organized in β-barrels  or β-PFT

These are hydrophilic proteins rich in β-sheets and most of the bacterial PFT belong to this class. β-PFTs bind to a cell surface receptor, oligomerize and one or two β-hairpins of individual monomers associate into a β-barrel structure which inserts into the lipid bilayer and creates a channel.