Pertussis toxin is a large protein produced by Bordatella pertussis, the causal agent of whooping cough. Also known as PT, the toxin is a large protein comprised of six subunits. It is an exotoxin and is released from the bacterial cells in an inactive form. Once taken up into cells, it is activated, disrupting the intracellular signaling mechanisms of its host cells and facilitating the bacterial colonization of the infected person. This bacterial disease is one of the contagious diseases that strikes both children and adults, despite the existence of a vaccine against the organism.
There are six subunits of pertussis toxin, known as S1, S2, S3, S4, and S5. There are two molecules of the S4 subunit in each molecule of PT. This type of toxin is known as an A/B toxin. The A part of pertussis toxin is comprised of S1, has enzymatic activity, and can catalyze chemical reactions.
The B section of PT contains subunits S2-S5, and bind to receptors on the host’s cell membrane. Once an appropriate compound binds to it, this triggers cellular activity. The binding of the B parts of pertussis toxin causes activation of the A subunit. Once this subunit is active, it interferes with the host's immune response.
An important part of the human immune system is the activation of receptors called G proteins. They stimulate many pathways involved in immunity. If their activity is blocked, this can greatly interfere with the ability to fend off a pathogenic attack. The activation of the pertussis toxin A subunit enables it to add ADP-ribose to one form of G protein, thus greatly hampering intracellular signaling and interfering with an immune response to infection with this Bordatella pathogen.
Pertussis toxin subunits S2 and S3 bind to receptors on different types of cells. Subunit 3 can bind to the surface of cells called phagocytes, whose function is to take in and absorb bacteria and other invaders. It is not clear why the pathogen triggers this response. One hypothesis is that by being inside these specialized cells, the pathogenic bacteria are able to limit another aspect of the immune system. Normally these cells would produce toxic oxidized products that would kill bacteria in the vicinity.
Biochemical research on G proteins frequently utilizes pertussis toxin, which is available commercially. The ability of this subunit to add ADP-ribose to the G protein causes its activity to be separate from any response of the G protein’s receptor. This is useful for studies of G proteins. It is available in an inactive form, and does not require activation if used with cell extracts or cells, but does when the experiments involve purified G protein.
