Pertussis Toxin-ATP Complex: Difference between revisions

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Jonathan Tringali, Jaime Prilusky, Michal Harel

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 <StructureSection load=1bcp size='500' side='right' caption='Pertussis Toxin-ATP complex ([[1bcp]])' scene=''>[[Image:230px-Pertussis.jpg|left|thumb|A young boy coughing due to pertussis.]]
-==introduction==
+==Introduction==
-'''Protussis Toxins''' is a major virulence factor of ''Bordetella pertussis'' that cause whooping cough.  Whooping cough, also known as pertusis, is a highly contagious bacterial disease caused by the bacteria ''Bordetella pertussis''.  This disease had been characterized by severe cough that has been documented to cause subconjunctival hemorrhages, rib fractures, hernias, fainting and vertebral artery dissection.  The pertussis toxin has been characterized as being a AB toxin meaning that there are 2 subunits: A subunit possesses the enzyme activity and the B subunit it the receptor binding portion.  Together this AB toxin colonizes the respiratory tract and becomes activated by destabilization due to the binding of ATP.
+'''Pertussis Toxins''' (PT) is a protein-based exotoxin and major virulence factor produced by the bacterium ''Bordetella pertussis.''  PT causes pertussis, which is also known at whooping cough and is highly contagious bacterial disease.  The disease is caused by the bacterium colonizing the respiratory tract where it then establishes an infection.  This disease had been characterized by severe coughing that can last up to six weeks and in some countries lasting nearly 100 days. It has been documented in some cases that PT can cause subconjunctival hemorrhages, rib fractures, hernias, fainting and vertebral artery dissection.
+As of 2010, the worldwide incidence of whooping cough has been estimated to 48.5 million cases and nearly 295,000 deaths per year.  With that in mind, whooping cough can affect people of any age; however, before vaccines were available the disease was most common in infants and young children but now children are immunized and the high percentage of cases are seen among adolescents.
 ==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_1/3'>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_2/3'>S2 (chains B,H)</scene>,
+The pertussis toxin has been characterized, as being an AB toxin meaning that there are 2 subunits: A subunit possesses the enzyme activity and the B subunit it the receptor binding portion.  PT in particular is an 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_1/3'>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_2/3'>S2 (chains B,H)</scene>,
-<scene name='Pertussis_Toxin-ATP_Complex/Subunit_3/5'>S3 (chains C,I)</scene>, two copies of <scene name='Pertussis_Toxin-ATP_Complex/Subunit_4/3'>S4 (chains D,E,J,K)</scene>, and <scene name='Pertussis_Toxin-ATP_Complex/Subunit_5/4'>S5 (chains F,L)</scene></scene>.<ref name=Hazes>PMID: 8637000</ref>  This B subnit is what binds to the terminal sialic acid residues.
+<scene name='Pertussis_Toxin-ATP_Complex/Subunit_3/5'>S3 (chains C,I)</scene>, two copies of <scene name='Pertussis_Toxin-ATP_Complex/Subunit_4/3'>S4 (chains D,E,J,K)</scene>, and <scene name='Pertussis_Toxin-ATP_Complex/Subunit_5/4'>S5 (chains F,L)</scene>.<ref name=Hazes>PMID: 8637000</ref>  These subunits are encoded by a ptx genes, which are encoded on a large PT operon that includes additional genes as well such as Pti genes.  Together the PT and Pti proteins form the PT secretion complex.
 ==Pertussis Toxin activation==
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 ==Treatment==
+Early treatment of pertussis is the only effective way to treat the bacterial infection.  If treatment for pertussis is started early in the course of illness during the 1 to 2 weeks before severe coughing occurs, the symptoms may be lessened.  If the diagnosed to late, antibiotics will not alter the course of the illness since the bacteria is already producing the PT toxin.  The preferred antibiotics are Erythromycin, clarithromycin, and azithromycin.
+The primary method of prevention for pertussis is vaccination.  The DTaP vaccine is used and this vaccine is composed of diphtheria, tetanus, and pertussis.  The pertussis component is acellular; the selected antigens of pertussis induce immunity.
 ==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. (talk about this more and clarify)
+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. The key features of this proposal is that ATP binding signals the arrival of the PT in the endoplasmic reticulum and at the same time triggers dissociation of the holotoxin prior to membrane translocation.  Therefore, the dissociation is due to ATP binding destabilization and reduction by protein disulphide isomerase.
 </StructureSection>