Toxicity of botulinum toxin type B (BoNT/B)

Stable Identifier
R-HSA-5250958
Type
Pathway
Species
Homo sapiens
Related Species
Clostridium botulinum
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Botulinum toxin type B (BoNT/B), a disulfide-bonded heavy chain (HC) - light chain (LC) heterodimer, 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) and multiple copies of three hemagglutinin proteins (HA, encoded by the C. botulinum ha17, ha34, and ha70 genes) (Amatsu 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 synaptotagmin (SYT) proteins exposed by exocytosis at a synapse of a target neuron (Dong et al. 2003; 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. Tthe HC - LC disulfide bond is reduced (Montal 2010). The LC then catalyzes the cleavage of vesicle-associated membrane protein 2 (VAMP2) on the cytosolic face of synaptic vesicle membranes (Foran et al. 1994; Schiavo et al. 1992), thereby inhibiting synaptic vesicle fusion with the plasma membrane and exocytosis.

Literature References
PubMed ID Title Journal Year
23239348 Uptake of botulinum neurotoxin in the intestine

Fujinaga, Y, Sugawara, Y, Matsumura, T

Curr. Top. Microbiol. Immunol. 2013
1331807 Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin

Schiavo, G, Benfenati, F, Poulain, B, Rossetto, O, Polverino de Laureto, P, DasGupta, BR, Montecucco, C

Nature 1992
14504267 Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells

Dong, M, Richards, DA, Goodnough, MC, Tepp, WH, Johnson, EA, Chapman, ER

J Cell Biol 2003
24165130 Crystal Structure of Clostridium botulinum Whole Hemagglutinin Reveals a Huge Triskelion-shaped Molecular Complex

Amatsu, S, Sugawara, Y, Matsumura, T, Kitadokoro, K, Fujinaga, Y

J. Biol. Chem. 2013
7803399 Differences in the protease activities of tetanus and botulinum B toxins revealed by the cleavage of vesicle-associated membrane protein and various sized fragments

Foran, P, Shone, CC, Dolly, JO

Biochemistry 1994
20233039 Botulinum neurotoxin: a marvel of protein design

Montal, M

Annu. Rev. Biochem. 2010
15514477 Glycosphingolipids-sweets for botulinum neurotoxin

Yowler, BC, Schengrund, CL

Glycoconj. J. 2004
15217342 The synaptic vesicle cycle

S├╝dhof, TC

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

Hatheway, CL

Curr. Top. Microbiol. Immunol. 1995
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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