Clostridium perfringens alpha toxin

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Clostridium perfringens alpha toxin
Clostridium perfringens Alpha Toxin.rsh.png
Crystal structure of Clostridium perfringens alpha toxin
Identifiers
Symbol ?
Alt. symbols phospholipase C, CPE0036, Zn_dep_PLPC
Entrez 988262
PDB 1CA1 (RCSB PDB PDBe PDBj) 1KHO, 1GYG, 1QM6, 1QMD, 1KHO, 1GYG, 1QM6, 1QMD
RefSeq NP_560952.1
Other data
EC number 3.1.4.3

Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.

Clinical significance[edit]

This toxin has been shown to be the key virulence factor in infection with C. perfringens; the bacterium is unable to cause disease without this toxin.[1] Further, vaccination against the alpha toxin toxoid protects mice against C. perfringens gas gangrene.[2] As a result, knowledge about the function of this particular protein greatly aids understanding of myonecrosis.

Structure and homology[edit]

The alpha toxin has remarkable similarity to toxins produced by other bacteria as well as natural enzymes. There is significant homology with phospholipase C enzymes from Bacillus cereus, C. bifermentans, and Listeria monocytogenes.[3] The C terminal domain shows similarity with non-bacterial enzymes such as pancreatic lipase, soybean lipoxygenase, and synaptotagmin I.[4]

The alpha toxin is a zinc metallophospholipase, requiring zinc for activation. First, the toxin binds to a binding site on the cell surface. The C-terminal C2-like PLAT domain binds calcium and allows the toxin to bind to the phospholipid head-groups on the cell surface. The C-terminal domain enters the phospholipid bilayer. The N-terminal domain has phospholipase activity. This property allows hydrolysis of phospholipids such as phosphatidyl choline, mimicking endogenous phospholipase C. The hydrolysis of phosphatidyl choline produces diacylglycerol, which activates a variety of second messenger pathways. The end-result includes activation of arachidonic acid pathway and production of thromboxane A2, production of IL-8, platelet-activating factor, and several intercellular adhesion molecules. These actions combine to cause edema due to increased vascular permeability.[3]

See also[edit]

References[edit]

  1. ^ Awad, M.M., Bryant, A.E., Stevens, D.L. & Rood, J.I. (1995). "Virulence studies on chromosomal alpha-toxin and alpha-toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of alpha-toxin in Clostridium perfringens-mediated gas gangrene". Mol Microbiol 15 (2): 191–202. doi:10.1111/j.1365-2958.1995.tb02234.x. PMID 7746141. 
  2. ^ Williamson ED & Titball RW. (1993). "A genetically engineered vaccine against the alpha-toxin of Clostridium perfringens also protects mice against experimental gas gangrene". Vaccine 11 (12): 1253–1258. doi:10.1016/0264-410X(93)90051-X. PMID 8256506. 
  3. ^ a b Sakurai J, Nagahama M, Oda M. (2004). "Clostridium perfringens Alpha-Toxin: Characterization and Mode of Action". J Biochem 136 (5): 569–574. doi:10.1093/jb/mvh161. PMID 15632295. 
  4. ^ Naylor CE, Eaton JT, Howells A, et al. (1998). "Structure of the key toxin in gas gangrene". Nature Structural & Molecular Biology 5 (8): 738–746. doi:10.1038/1447. PMID 9699639. 

External links[edit]