User:Caitlin Bell/Sandbox 1
From Proteopedia
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The A subunit is the most destructive part of the cholera toxin. It can be further broken down into two chains: A1 and A2. These chains are held together through a single disulfide bond. The A1 chain is entirely non-polar, which allows it to pass through the intestinal membrane and into the cell. The A1 chain has a <scene name='User:Caitlin_Bell/Sandbox_1/Catalytic_site/1'>binding site</scene> for NAD+, and when bound, begins the downstream events that ultimately leads to the Cholera disease. The A2 chain’s main function is to connect the A1 chain to the B subunit. | The A subunit is the most destructive part of the cholera toxin. It can be further broken down into two chains: A1 and A2. These chains are held together through a single disulfide bond. The A1 chain is entirely non-polar, which allows it to pass through the intestinal membrane and into the cell. The A1 chain has a <scene name='User:Caitlin_Bell/Sandbox_1/Catalytic_site/1'>binding site</scene> for NAD+, and when bound, begins the downstream events that ultimately leads to the Cholera disease. The A2 chain’s main function is to connect the A1 chain to the B subunit. | ||
| - | The B subunit’s only function is to allow the cholera toxin to enter the intestinal epithelial cells through endocytosis. It accomplishes this from its unique structure. The B subunit contains five alpha helix proteins that are connected together to form a pentagon. Each alpha helix contains a single binding site for the intestinal lining, which is called its <scene name='User:Caitlin_Bell/Sandbox_1/Gm1_binding_sites/ | + | The B subunit’s only function is to allow the cholera toxin to enter the intestinal epithelial cells through endocytosis. It accomplishes this from its unique structure. The B subunit contains five alpha helix proteins that are connected together to form a pentagon. Each alpha helix contains a single binding site for the intestinal lining, which is called its <scene name='User:Caitlin_Bell/Sandbox_1/Gm1_binding_sites/2'>GM1 binding site</scene> (monosialoganglioside binding site). |
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The mechanism of action of the cholera toxin can be broken down into three simple stages: entry of the toxin into the cell, activation of the G protein through its catalytic functions, and efflux of ions. | The mechanism of action of the cholera toxin can be broken down into three simple stages: entry of the toxin into the cell, activation of the G protein through its catalytic functions, and efflux of ions. | ||
| - | First, after ingestion of ''Vibrio cholerae'', the cholera toxin is secreted in the intestines. Once inside, the B subunit binds to the intestinal wall through its<scene name='User:Caitlin_Bell/Sandbox_1/Gm1_binding_sites/ | + | First, after ingestion of ''Vibrio cholerae'', the cholera toxin is secreted in the intestines. Once inside, the B subunit binds to the intestinal wall through its <scene name='User:Caitlin_Bell/Sandbox_1/Gm1_binding_sites/2'>GM1 binding sites</scene>. The cholera toxin is then engulfed by the intestinal epithelial cell through endocytosis, and immediately following, the A subunit is cleaved at its disulfide bond to release the A1 chain. |
Second, after the A1 chain is released inside the intestinal cell, it binds NAD+ at its <scene name='User:Caitlin_Bell/Sandbox_1/Catalytic_site/1'>catalytic site</scene> and removes an ADP-ribose from it, and proceeds to transfer this to a stimulatory G protein. This transfer is called an ADP-ribosylation reaction. | Second, after the A1 chain is released inside the intestinal cell, it binds NAD+ at its <scene name='User:Caitlin_Bell/Sandbox_1/Catalytic_site/1'>catalytic site</scene> and removes an ADP-ribose from it, and proceeds to transfer this to a stimulatory G protein. This transfer is called an ADP-ribosylation reaction. | ||
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Third, once the stimulatory G protein is bound to an ADP-ribose, it is permanently active. This means that it is unable to hydrolyze its GTP, which would normally allow the protein to “switch off”. Thus, the stimulatory G protein continually activates adenylyl cyclase, which leads to a constant production of cAMP. Consequently, cAMP activates Protein Kinase A, which activates the CFTR-regulated Cl- channel. Constant activation of this ion channel results in an enormous efflux of ions and water from the cell to the interstitial lumen, which is representative of the symptomatic excessive diarrhea in Cholera. | Third, once the stimulatory G protein is bound to an ADP-ribose, it is permanently active. This means that it is unable to hydrolyze its GTP, which would normally allow the protein to “switch off”. Thus, the stimulatory G protein continually activates adenylyl cyclase, which leads to a constant production of cAMP. Consequently, cAMP activates Protein Kinase A, which activates the CFTR-regulated Cl- channel. Constant activation of this ion channel results in an enormous efflux of ions and water from the cell to the interstitial lumen, which is representative of the symptomatic excessive diarrhea in Cholera. | ||
| - | <scene name='User:Caitlin_Bell/Sandbox_1/Gm1_binding_sites/2'>TextToBeDisplayed</scene> | ||
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Revision as of 01:07, 26 April 2011
Contents |
CHOLERA TOXIN
Introduction
Cholera toxin is released by the pathogen Vibrio cholerae during colonization of the small intestine. The genus Vibrio mainly corresponds with saltwater organisms, but there are some freshwater organisms. These organisms use glucose as their main energy and fuel source, and they use flagella for locomotion.
Cholera is widespread in mainly poverty-stricken areas where food and water environments are unsanitary. After ingestion of Vibrio cholerae, which typically is a result of feces particles in water or food, the cholera toxin is secreted and infects the small intestines, leading to the Cholera disease. Excessive diarrhea and vomiting ensues soon after ingestion, and death can occur within a few hours. Cholera is mainly prevalent in Africa, Asia, and Latin America, leading to 3-5 million cases and 100,000-200,000 deaths every year.
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Structure
The fundamental structure of the cholera toxin is rather basic. It is a complex of six proteins that are structured into two subunits: A and B. The A subunit contains only one protein and is the only toxic part of the protein. The B subunit contains five proteins and is non-toxic.
The A subunit is the most destructive part of the cholera toxin. It can be further broken down into two chains: A1 and A2. These chains are held together through a single disulfide bond. The A1 chain is entirely non-polar, which allows it to pass through the intestinal membrane and into the cell. The A1 chain has a for NAD+, and when bound, begins the downstream events that ultimately leads to the Cholera disease. The A2 chain’s main function is to connect the A1 chain to the B subunit.
The B subunit’s only function is to allow the cholera toxin to enter the intestinal epithelial cells through endocytosis. It accomplishes this from its unique structure. The B subunit contains five alpha helix proteins that are connected together to form a pentagon. Each alpha helix contains a single binding site for the intestinal lining, which is called its (monosialoganglioside binding site).
Mechanism of Action
The mechanism of action of the cholera toxin can be broken down into three simple stages: entry of the toxin into the cell, activation of the G protein through its catalytic functions, and efflux of ions.
First, after ingestion of Vibrio cholerae, the cholera toxin is secreted in the intestines. Once inside, the B subunit binds to the intestinal wall through its . The cholera toxin is then engulfed by the intestinal epithelial cell through endocytosis, and immediately following, the A subunit is cleaved at its disulfide bond to release the A1 chain.
Second, after the A1 chain is released inside the intestinal cell, it binds NAD+ at its and removes an ADP-ribose from it, and proceeds to transfer this to a stimulatory G protein. This transfer is called an ADP-ribosylation reaction.
Third, once the stimulatory G protein is bound to an ADP-ribose, it is permanently active. This means that it is unable to hydrolyze its GTP, which would normally allow the protein to “switch off”. Thus, the stimulatory G protein continually activates adenylyl cyclase, which leads to a constant production of cAMP. Consequently, cAMP activates Protein Kinase A, which activates the CFTR-regulated Cl- channel. Constant activation of this ion channel results in an enormous efflux of ions and water from the cell to the interstitial lumen, which is representative of the symptomatic excessive diarrhea in Cholera.
