Toxicity of botulinum toxin type E (BoNT/E)

Stable Identifier
R-HSA-5250992
Type
Pathway
Species
Homo sapiens
Related Species
Clostridium botulinum
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Botulinum toxin type E (BoNT/E), a disulfide-bonded heavy chain (HC) - light chain (LC) heterodimer (“dichain”), enters the gut typically as a result of consuming contaminated food (Hatheway 1995), as a complex with nontoxic nonhemagglutinin protein (NTNHA, encoded by the C. botulinum ntnha gene) (Benefield et al. 2013). The complex protects the toxin from degradation in the gut and mediates its association with the gut epithelium and transcytosis to enter the circulation (Fujinaga et al. 2013). Circulating toxin molecules associate with gangliosides and synaptic vesicle protein 2 (SV2) exposed by exocytosis at a synapse of a target neuron (Dong et al. 2008; Yowler & Schengrund 2004). Vesicle recycling brings the toxin into the neuron where the vesicle is acidified (Sudhoff 2004). The lowered pH induces a conformational change in the toxin: its HC forms a passage in the vesicle membrane through which its LC is extruded into the neuronal cytosol and released by reduction of the HC - LC disulfide bond (Montal 2010). The LC then catalyzes the cleavage of synaptosome-associated protein 25 (SNAP25) on the cytosolic face of the neuronal plasma membrane (Binz et al. 1994; Schiavo et al. 1993), thereby inhibiting synaptic vesicle fusion with the plasma membrane and exocytosis.

Literature References
PubMed ID Title Journal Year
20233039 Botulinum neurotoxin: a marvel of protein design

Montal, M

Annu. Rev. Biochem. 2010
23239348 Uptake of botulinum neurotoxin in the intestine

Fujinaga, Y, Sugawara, Y, Matsumura, T

Curr. Top. Microbiol. Immunol. 2013
15514477 Glycosphingolipids-sweets for botulinum neurotoxin

Yowler, BC, Schengrund, CL

Glycoconj. J. 2004
8243676 Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds

Schiavo, G, Santucci, A, DasGupta, BR, Mehta, PP, Jontes, J, Benfenati, F, Wilson, MC, Montecucco, C

FEBS Lett 1993
15217342 The synaptic vesicle cycle

Südhof, TC

Annu Rev Neurosci 2004
8542759 Botulism: the present status of the disease

Hatheway, CL

Curr. Top. Microbiol. Immunol. 1995
23509303 Molecular assembly of botulinum neurotoxin progenitor complexes

Benefield, DA, Dessain, SK, Shine, N, Ohi, MD, Lacy, DB

Proc. Natl. Acad. Sci. U.S.A. 2013
18815274 Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons

Dong, M, Liu, H, Tepp, WH, Johnson, EA, Janz, R, Chapman, ER

Mol. Biol. Cell 2008
8294407 Proteolysis of SNAP-25 by types E and A botulinal neurotoxins

Binz, T, Blasi, J, Yamasaki, S, Baumeister, A, Link, E, Südhof, TC, Jahn, R, Niemann, H

J Biol Chem 1994
Participants
Participant Of
Disease
Name Identifier Synonyms
botulism 11976 Botulism (disorder), Intoxication with Clostridium botulinum toxin, Botulism, Infection due to clostridium botulinum, Botulism, Foodborne botulism, botulism, Botulism, Botulism, Botulism, Food poisoning due to Clostridium botulinum, Botulism poisoning
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