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

Stable Identifier
R-HSA-5244506
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Clostridium botulinum
Compartment
synaptic vesicle membrane, cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
botE HC transports botE LC from target cell synaptic vesicle membrane into cytosol
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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 E disulfide bonded heavy chain - light chain dimer (botE 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. 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
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 botE:SV2:GT1b [synaptic vesicle membrane]

Physical Entity
botE:SV2: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  (2014-01-19)
Cite Us!