Cholera toxin: Difference between revisions
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[[Image:CTX interaction.PNG|left|270px|thumb| Interaction of 7 chains of Cholera toxin[[1xtc]]. Cholera toxin contains 7 chains: A,C,D,E,F,G and H.Chains A and C belong to subunit A. Chains C,D,E,F,G and H belong to subunit B]] | [[Image:CTX interaction.PNG|left|270px|thumb| Interaction of 7 chains of Cholera toxin[[1xtc]]. Cholera toxin contains 7 chains: A,C,D,E,F,G and H.Chains A and C belong to subunit A. Chains C,D,E,F,G and H belong to subunit B]] | ||
Cholera toxin(CTX) has two types of subunits: subunit A and subunit B. A subunit contains A1 domain, which includes the enzymatic active site, and A2 domain, which has a α–helix tail. The B subunit contains five chains that form a pentameric ring around the central pore in structure; Subunit A and subunit B are assembled by the α–helix tail of A2 domain, which inserts into the central pore. CTX is the main virulence factor of the pathogen ''Vibrio cholerae'' and cause the major symptom of infection: extreme diarrhea, vomiting, cramps and even death [1][2][3]. | Cholera toxin(CTX) has two types of subunits: subunit A and subunit B. A subunit contains A1 domain, which includes the enzymatic active site, and A2 domain, which has a α–helix tail. The B subunit contains five chains that form a pentameric ring around the central pore in structure; Subunit A and subunit B are assembled by the α–helix tail of A2 domain, which inserts into the central pore. CTX is the main virulence factor of the pathogen ''Vibrio cholerae'' and cause the major symptom of infection: extreme diarrhea, vomiting, cramps and even death [1][2][3]. | ||
The enzymatic subunit has a globular domain (CTA1) and a long helical domain (CTA2). Once the CTX binds to the cell surface, it is internalized, and its CTA1 domain binds to ADP-ribosylation factor 6 (Arf6) enabling its catalytic activity. | The enzymatic subunit has a globular domain (CTA1) and a long helical domain (CTA2). Once the CTX binds to the cell surface, it is internalized, and its CTA1 domain binds to ADP-ribosylation factor 6 (Arf6), enabling its catalytic activity. | ||
The image at the lower right correspond to the crystal structure of cholera toxin ([[1xtc]]). The image at left correspond to the annotated interaction of 7 chains of cholera toxins([[1xtc]]) in Proteopedia see [[Toxins]]. | The image at the lower right correspond to the crystal structure of cholera toxin ([[1xtc]]). The image at left correspond to the annotated interaction of 7 chains of cholera toxins([[1xtc]]) in Proteopedia see [[Toxins]]. | ||
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== Function == | == Function == | ||
Cholera toxin, after secreted from the ''Vibrio cholerae'', binds to the enterocytes (intestinal cells) by the interaction between the subunit B and GM1 ganglioside receptor on enterocytes, which then promotes the toxin endocytosis. Next, A1 turns to an active enzyme after separating with the A2 domain. After A1 domain of subunit A of toxin enters the cytosol, it activates | Cholera toxin, after being secreted from the ''Vibrio cholerae'', binds to the enterocytes (intestinal cells) by the interaction between the subunit B and GM1 ganglioside receptor on enterocytes, which then promotes the toxin endocytosis. Next, A1 turns to an active enzyme after separating with the A2 domain. After the A1 domain of subunit A of the toxin enters the cytosol, it activates adenylate cyclase to produce cAMP through G proteins, which triggers the activation of cystic fibrosis transmembrane conductance regulator (CFTR), leading to watery diarrhea: the efflux of water and ions from cells [3]. | ||
== Evolution == | == Evolution == | ||
CTXφ Bacteriophage | CTXφ Bacteriophage which is carried by ''Vibrio cholerae'' produces Cholera toxin. Cholera toxin is encoded by the ctxA and ctxB genes that are introduced into V. cholerae strains by horizontal gene transfer [4]. | ||
== Application == | == Application == | ||