Sandbox Reserved 818: Difference between revisions
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==Mechanism of pertussis toxin== | ==Mechanism of pertussis toxin== | ||
Pertussis toxin (PTX) acts on target cells through its A protomer which contains the enzymatically active S1 subunit. | Pertussis toxin (PTX) acts on target cells through its A protomer which contains the enzymatically active S1 subunit. <br /> | ||
This subunit catalyzes ADP-ribosylation of the α-subunit of trimeric G proteins, which disturbs functions of the target cells and therefore lead to various biological effects. | This subunit catalyzes ADP-ribosylation of the α-subunit of trimeric G proteins, which disturbs functions of the target cells and therefore lead to various biological effects. | ||
In facts, substrates of PTX are regulators of the membrane-bound adenylate cyclase. These G proteins bind GTP in order to transduce signals in the cell. When ADP-ribosylation by PTX occurs, the downregulation of the adenylate cyclase activity is inhibited. | In facts, substrates of PTX are regulators of the membrane-bound adenylate cyclase. These G proteins bind GTP in order to transduce signals in the cell. When ADP-ribosylation by PTX occurs, the downregulation of the adenylate cyclase activity is inhibited. <br /> | ||
This inhibition leads to increase cAMP levels in cells, which explains the amount of biological activities of the toxin. | This inhibition leads to increase cAMP levels in cells, which explains the amount of biological activities of the toxin. | ||
-> picture of the active site of the S1 subunit | -> picture of the active site of the S1 subunit <br /> | ||
labeled in green : key residues surrounding the NAD-binding cavity (Arg9, Trp26, Cys41) | labeled in green : key residues surrounding the NAD-binding cavity (Arg9, Trp26, Cys41) <br /> | ||
labeled in blue : catalytic residues (His35, Glu129) | labeled in blue : catalytic residues (His35, Glu129) <br /> | ||
PTX-catalysed ADP-ribosylation | PTX-catalysed ADP-ribosylation | ||
