Cholera toxin: Difference between revisions
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== Structure == | == Structure == | ||
[[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 | 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 <ref>Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. p. 375. ISBN 0838585299.</ref>,<ref>Faruque SM; Nair GB (editors). (2008). Vibrio cholerae: Genomics and Molecular Biology. Caister Academic Press. ISBN 978-1-904455-33-2.</ref>,<ref>Jennifer McDowall, Cholera Toxin, EMBL-EMI, Interpro</ref>. | ||
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. | ||
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== Function == | == Function == | ||
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 | 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 <ref>Jennifer McDowall, Cholera Toxin, EMBL-EMI, Interpro</ref>. | ||
== Evolution == | == Evolution == | ||
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 | 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 <ref>Davis B, Waldor M (2003). "Filamentous phages linked to virulence of Vibrio cholerae". Curr Opin Microbiol 6 (1): 35–42. doi:10.1016/S1369-5274(02)00005-X. PMID 12615217.</ref>. | ||
== Application == | == Application == | ||
Subunit B of cholera toxin is designed to be applied as a neuronal tracer due to its non-toxic characteristic. It also used to identify lipid rafts as florescent tag on the cell surface since lipid rafts contains GM1 gangliosides, which will interact with subunit B during mechanism | Subunit B of cholera toxin is designed to be applied as a neuronal tracer due to its non-toxic characteristic. It also used to identify lipid rafts as florescent tag on the cell surface since lipid rafts contains GM1 gangliosides, which will interact with subunit B during mechanism <ref>Luppi P.H.. "The Discovery of Cholera-Toxin as a Powerful Neuroanatomical Tool". Retrieved 2011-03-23.</ref>. It is demonstrated that cholera toxin subunit B is a sensitive retrograde tracer for the central nervous system <ref>Luppi P.H., Fort P., Jouvet M. Iontophoretic application of unconjugated cholera toxin B subunit (CTb) combined with immunohistochemistry of neurochemical substances: a method for transmitter identification of retrogradely labeled neurons. Brain Res. 534 (1-2) pages : 209-224 (1990)</ref>. | ||
== 3D Structures of Cholera toxin == | == 3D Structures of Cholera toxin == | ||
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== Multiple Sequence Alignment == | == Multiple Sequence Alignment == | ||
[[Image:MSA1.jpg|left| | [[Image:MSA1.jpg|left|250px|thumb|Multiple Sequence Alignment-TEXSHADE result.BlastP of CTX A subunit that contains six different species. This is made by Biology Workbench]] | ||
'''Selected Sequences:''' | '''Selected Sequences:''' | ||
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== Reference == | == Reference == | ||
<references /> | |||
== External Links == | == External Links == | ||