Cholera toxin
| Cholera toxin, subunit A. | ||
|---|---|---|
|
Existing structural data: s. UniProt |
||
| Mass / length primary structure | 242 = 194 + 46 amino acids | |
| Secondary to quaternary structure | α1 + α2 | |
| Identifier | ||
| Gene name (s) | ctxA (KEGG) | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 2.4.2.36 , transferase | |
| Response type | Transfer of an ADP ribosyl residue | |
| Substrate | NAD + + peptide Diphthamide | |
| Products | Nicotinamide + peptide-N-ADP-ribosyldiphtamide | |
| Cholera toxin, subunit B | ||
|---|---|---|
|
Existing structural data: s. UniProt |
||
| Mass / length primary structure | 103 amino acids | |
| Identifier | ||
| Gene name (s) | ctxB (KEGG) | |
| External IDs | ||
The cholera toxin ( CTX ) is one of the bacterium Vibrio cholerae (both the classical biovar as well as the biovar El Tor) produced exotoxin that a serious human diarrheal disease can cause. The enterotoxin triggers cholera . It was discovered by Sambhu Nath De in 1959 .
Mechanism of action
Cholera toxin is a hexameric protein made up of one α and five β subunits. It crosses the plasma membrane and inhibits the GTPase activity of the G αs subunit of a heterotrimeric G protein by ADP-ribosylating it (from intracellular NAD ) . As a result, the intrinsic GTPase activity of the G αs subunit, which converts GTP to GDP, is blocked - the G protein remains in the active state. It now permanently activates the adenylate cyclase, there is an excess of the second messenger cAMP . This changes the activity of certain membrane channels.
Pathophysiological effect on the intestinal epithelium
The permanently increased cAMP leads to increased incorporation of the chloride channel Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) into the membrane and thus to an increased loss of Cl - ions in the lumen. In addition, there is a Na + -loss by inhibiting the Na + / H + -Austauschers (NHE3) and the Na + In channel ( epithelial sodium channel , ENaC), that for the Na + is responsible -Rückresorption into the epithelium. It is also assumed that the tight junctions permeability between the epithelial cells increases. As a result, dehydration and electrolyte deficiency result from the loss of NaCl and the withdrawal of H 2 O from the epithelium, which passively follows the NaCl into the intestinal lumen. It can cause severe diarrhea with water losses of up to one liter per hour come also to massive efflux of potassium - and bicarbonate - ions through the intestines.
Overall, this leads to the clinical picture of cholera . The cholera toxin is part of a cholera vaccine .
literature
- Bruce Alberts , A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter: Molecular Biology of the Cell. Fifth edition, reference edition, Garland Science, New York 2008.
Web links
- The cholera toxin - structure and mode of action
- Jennifer McDowall / Interpro: Protein Of The Month: Cholera toxin. (English)
- Cholera Enterotoxin Vibrio cholerae - VC1457 in the Kyoto Encyclopedia of Genes and Genomes
Individual evidence
- ^ Joaquín Sánchez, Jan Holmgren: Cholera toxin - A foe & a friend . In: The Indian Journal of Medical Research . tape 133 , no. 2 , February 2011, ISSN 0971-5916 , p. 153-163 , PMID 21415489 , PMC 3089046 (free full text).