Pertussis Toxin-ATP Complex: Difference between revisions
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==structure== | ==structure== | ||
The protussis toxin is a AB5 toxin consisting of a six-component protein complex. With that in mind, this protein is a hexamer containing a catalytic (S1) subunit that is tightly associated with the pentameric cell-binding component (B-oligomer). The S1 component is a single subunit <scene name='Pertussis_Toxin-ATP_Complex/Subunit_1/2'>(S1):chains A,G</scene> while the B-oligomer is a pentamer composed of four types of subunits: <scene name='Pertussis_Toxin-ATP_Complex/Subunit_2/2'>S2 (chains B,H)</scene>, <scene name='Pertussis_Toxin-ATP_Complex/Subunit_3/2'>S3 (chainsC,I)</scene>, two copies of <scene name='Pertussis_Toxin-ATP_Complex/Subunit_4/2'>S4 (chains D,E,J,K)</scene>, and <scene name='Pertussis_Toxin-ATP_Complex/Subunit_5/3'>S5 (chains F,L)</scene>. This B subnit is what binds to the terminal sialic acid residues. | The protussis toxin is a AB5 toxin consisting of a six-component protein complex. With that in mind, this protein is a hexamer containing a catalytic (S1) subunit that is tightly associated with the pentameric cell-binding component (B-oligomer). The S1 component is a single subunit <scene name='Pertussis_Toxin-ATP_Complex/Subunit_1/2'>(S1):chains A,G</scene> while the B-oligomer is a pentamer composed of four types of subunits: <scene name='Pertussis_Toxin-ATP_Complex/Subunit_2/2'>S2 (chains B,H)</scene>, <scene name='Pertussis_Toxin-ATP_Complex/Subunit_3/2'>S3 (chainsC,I)</scene>, two copies of <scene name='Pertussis_Toxin-ATP_Complex/Subunit_4/2'>S4 (chains D,E,J,K)</scene>, and <scene name='Pertussis_Toxin-ATP_Complex/Subunit_5/3'>S5 (chains F,L)</scene>.<ref name=Hazes> This B subnit is what binds to the terminal sialic acid residues. | ||
==Pertussis Toxin activation== | ==Pertussis Toxin activation== | ||
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Following the pertussis toxin binding to the cell membrane, the toxin is taken up by an endosome and transported from the plasma membrane via the Golgi apparatus to the endoplasmic reticulum (ER) where finally membrane translocation occurs. The destabilization of PT occurs in the ER prior to membrane translocation. After binding of ATP, cleavage of the single disulphide bond in subunit S1 <scene name='Pertussis_Toxin-ATP_Complex/Disulphide_bonds_breaking/1'>(Cys 41-Cys 201)</scene> is believed to trigger a conformational change necessary to expose the active site to its substrates. The reducation step takes place after interaction of PT with ATP. After destabilization, the S1 becomes active and catalyzes the ADP-ribosylation of the alpa-subunit of regulatory trimeric G-proteins (Gialpha). This then prevents Gialpha from inhibiting adenylate cyclase and leads to an increase in intracellular levels of cyclic AMP (cAMP). The increase in cAMP affects normal biological signaling and causes severe effects such as hypoglycemia. | Following the pertussis toxin binding to the cell membrane, the toxin is taken up by an endosome and transported from the plasma membrane via the Golgi apparatus to the endoplasmic reticulum (ER) where finally membrane translocation occurs. The destabilization of PT occurs in the ER prior to membrane translocation. After binding of ATP, cleavage of the single disulphide bond in subunit S1 <scene name='Pertussis_Toxin-ATP_Complex/Disulphide_bonds_breaking/1'>(Cys 41-Cys 201)</scene> is believed to trigger a conformational change necessary to expose the active site to its substrates. The reducation step takes place after interaction of PT with ATP. After destabilization, the S1 becomes active and catalyzes the ADP-ribosylation of the alpa-subunit of regulatory trimeric G-proteins (Gialpha). This then prevents Gialpha from inhibiting adenylate cyclase and leads to an increase in intracellular levels of cyclic AMP (cAMP). The increase in cAMP affects normal biological signaling and causes severe effects such as hypoglycemia. | ||
== | ==Conclusion== | ||
This paper was significant since it gave a clear understanding of the PT activation as well as a better understanding to the pathogenesis of the toxin. | This paper was significant since it gave a clear understanding of the PT activation as well as a better understanding to the pathogenesis of the toxin. | ||
==References== | |||
{{Reflist}} | |||