Cholera toxin

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Cholera toxin 1xtc
Structural annotation: Resources: CATH : 1Xtca00, 1Xtcc00, 1Xtcd00, 1Xtce00, 1Xtcf00, 1Xtcg00, 1Xtch00 InterPro : Ipr000886, Ipr001144, Ipr008992, Ipr001835 Pfam : PF01375, PF01376 SCOP : d1xtc.1, d1xtcd_, d1xtce_, d1xtcf_, d1xtcg_, d1xtch_ UniProt : P01555, P01556
Functional annotation: Cellular component: extracellular region membrane Biological process: pathogenesis Molecular function: NAD+-diphthamide ADP-ribosyltransferase activity transferase activity, transferring glycosyl groups transferase activity catalytic activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Cholera toxin (CTX), secreted by bacterium Vibrio Cholerae,is an oligomeric complex of an enzymatic subunit (chain A) and 5 copies of chain B which bind to the cell surface. CTX is the main cause of the diarrhea symptoms of cholera infection.

StructureStructure

File:1xtc bio r 500.jpg

Assumed Biological Structure of Cholera toxin 1xtc

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 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 images at the left and at the right correspond to the crystal structure of cholera toxin (1xtc). The images at the lower left correspond to the assumed biological molecule structure (1xtc) toxins in Proteopedia see Toxins.

File:1xtc.png

Crystal Structure of Cholera toxin 1xtc

mRNA StructuremRNA Structure

FunctionFunction

Cholera toxin, after secreted from the Vibrio cholera, 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 the adenylate cyclase to produce cAMP through G protein, which triggers the activation of cystic fibrosis transmembrane conductance regulator (CFTR), leading to watery diarrhea: the efflux of water and ions from cells [3].

EvolutionEvolution

CTXφ Bacteriophage that is carried by Vibrio cholera produces Cholera toxin. Cholera toxin is encoded by the gene which developed into Vibrio cholera by horizontal transfer [4].

ApplicationApplication

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 [5].

3D Structures of Cholera toxin3D Structures of Cholera toxin

Updated November 2011

CTXCTX

1xtc - CTX

CTX A subunitCTX A subunit

2a5d, 2a5g – CTX A subunit+hArf6+GTP – human
2a5f - CTX A subunit+hArf6+GTP+NAD
1s5b, 1s5c, 1s5d, 1s5e, 1s5f - CTX A subunit (mutant)

CTX B subunitsCTX B subunits

1fgb - CTX B subunits
1g8z , 1chp, 1chq - CTX B subunits (mutant)
1rcv, 1rd9, 1rdp, 1rf2, 1pzi, 1pzj, 1pzk, 1efi, 1eef, 1djr, 1eei – CTX B subunits+ galactoside derivatives
1llr, 1jqy, 1jr0, 1fd7, 1md2 - CTX B subunits+BMSC derivatives
1eef - CTX B subunits+PEPG
3chb, 2chb - CTX B subunits+pentasaccharide
1ct1 - CTX B subunits (mutant)+pentasaccharide
3efx – CTX B/heat-labile enterotoxin B chain
1tet – CTX peptide 3+FAB light and heavy chains - mouse

Multiple Sequence AlignmentMultiple Sequence Alignment

BlastP of CTX A subunit

Selected Sequences:

1. Cholera toxin Subunit A

2. Escherichia coli E24377A plasmid pETEC_80, complete sequence

3. Escherichia coli strain 214-III elt operon, complete sequence

4. Vibrio cholerae strain JS9803 prophage Vibrio phage CTX Zot (zot)

5. Vibrio cholera O395 chromosome II, complete sequence

6. Vibrio cholera O1 str. 2010EL-1786 chromosome 1, complete

ReferenceReference

[1] Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. p. 375. ISBN 0838585299.

[2] Faruque SM; Nair GB (editors). (2008). Vibrio cholerae: Genomics and Molecular Biology. Caister Academic Press. ISBN 978-1-904455-33-2 .

[3] Jennifer McDowall, Cholera Toxin, EMBL-EMI, Interpro

[4] 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.

[5] Pierre-Hervé Luppi. "The Discovery of Cholera-Toxin as a Powerful Neuroanatomical Tool". Retrieved 2011-03-23.