botB HC transports botB LC from target cell synaptic vesicle membrane into cytosol

Stable Identifier
R-HSA-5244404
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Clostridium botulinum
Compartment
synaptic vesicle membrane, cytosol
ReviewStatus
5/5
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botB HC transports botB LC from target cell synaptic vesicle membrane into cytosol
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By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type B disulfide bonded heavy chain - light chain dimer (botB HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved. Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2011, 2012).
Literature References
PubMed ID Title Journal Year
22720883 Botulinum neurotoxins B and E translocate at different rates and exhibit divergent responses to GT1b and low pH

Tepp, WH, Chapman, ER, Sun, S, Johnson, EA

Biochemistry 2012
20233039 Botulinum neurotoxin: a marvel of protein design

Montal, M

Annu. Rev. Biochem. 2010
21925111 Receptor binding enables botulinum neurotoxin B to sense low pH for translocation channel assembly

Liu, H, Tepp, WH, Chapman, ER, Sun, S, Suresh, S, Edwardson, JM, Johnson, EA

Cell Host Microbe 2011
12459720 Translocation of botulinum neurotoxin light chain protease through the heavy chain channel

Koriazova, LK, Montal, M

Nat Struct Biol 2003
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein transmembrane transporter activity of botB HC:LC:SYT:GT1b [synaptic vesicle membrane]

Physical Entity
botB HC:LC:SYT:GT1b [synaptic vesicle membrane] (Homo sapiens)
Activity
protein transmembrane transporter activity (GO:0008320)
This event is regulated
Positively by
Regulator
H+ [synaptic vesicle lumen]
Disease
Name Identifier Synonyms
botulism DOID: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
Authored
Gopinathrao, G  (2006-06-15)
Krupa, S  (2006-06-15)
Reviewed
Ichtchenko, K  (2007-08-03)
Thirunavukkarasu, N  (2014-11-18)
Sharma, S  (2014-11-18)
Created
D'Eustachio, P  (2014-01-18)
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