Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis. PT is involved in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments including hypertension, viral inhibition, and autoimmune inhibition.
Mechanism of pathogenesis
PT is an exotoxin with six subunits (named S1 through S5—each complex contains two copies of S4). The subunits are arranged in a A-B structure: the A component is enzymatically active and is formed from the S1 subunit, while the B component is the receptor-binding portion and is made up of subunits S2–S5. The subunits are encoded by ptx genes encoded on a large PT operon that also includes additional genes which encode Ptl proteins: Together these proteins form the PT secretion complex.
PT is released from B. pertussis in an inactive form. When the B subunit binds to a cell membrane receptor, the A subunit (or protomer) becomes activated, perhaps through the action of glutathione and ATP. PT catalyzes the ADP-ribosylation of the α subunits of the heterotrimeric guanine nucleotide regulatory proteins Gi, Go, and Gt. This prevents the G-proteins from interacting with cell membrane receptors, thus interfering with intracellular communication. Since the Gα subunits remain in their GDP-bound, inactive state, they are unable to inactivate adenylyl cyclase or open potassium channels.
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