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.
- ↑ Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill. ISBN 0-8385-8529-9.
- ↑ Kost C, Herzer W, Li P, Jackson E (1999). "Pertussis toxin-sensitive G-proteins and regulation of blood pressure in the spontaneously hypertensive rat". Clin Exp Pharmacol Physiol 26 (5-6): 449-55. PMID 10386237.
- ↑ Alfano M, Pushkarsky T, Poli G, Bukrinsky M (2000). "The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages". J Virol 74 (18): 8767-70. PMID 10954581.
- ↑ Bagley K, Abdelwahab S, Tuskan R, Fouts T, Lewis G (2002). "Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway". J Leukoc Biol 72 (5): 962-9. PMID 12429718.
- ↑ 5.0 5.1 Locht C, Antoine R (1995). "A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit". Biochimie 77 (5): 333-40. PMID 8527486.
- ↑ Weiss A, Johnson F, Burns D (1993). "Molecular characterization of an operon required for pertussis toxin secretion". Proc Natl Acad Sci U S A 90 (7): 2970-4. PMID 8464913.
- ↑ Finger H, von Koenig CHW (1996). Bordetella. In: Barron's Medical Microbiology (Barron S et al, eds.), 4th ed., Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.
- ↑ Burns D (1988). "Subunit structure and enzymic activity of pertussis toxin". Microbiol Sci 5 (9): 285-7. PMID 2908558.
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