DT fragment B transports DT fragment A from target cell endosome membrane

Stable Identifier
R-HSA-5336420
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Corynephage beta
Compartment
cytosol, endocytic vesicle membrane
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DT fragment B transports DT fragment A from target cell endosome membrane
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The normal process of acidification of the endocytic vesicle containing diphtheria toxin (DT A:B) associated with target cell proteins HBEGF and CD9 is thought to cause a conformational change in the toxin. Its B fragment forms a channel in the endocytic vesicle membrane through which the A fragment is extruded into the target cell cytosol. There, reduction of the disulfide bond connecting the A and B fragments releases the A fragment to refold. The process requires participation of target cell heat shock proteins (HSP90AA1 and HSP90AB1) and thioredoxin reductase 1 (TXNRD1), which may mediate disulfide bond cleavage (Ratts et al. 2003; Murphy 2011).

Literature References
PubMed ID Title Journal Year
12668662 The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

Ratts, R, Zeng, H, Berg, EA, Blue, C, McComb, ME, Costello, CE, vanderSpek, J, Murphy, JR

J. Cell Biol. 2003
22069710 Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process

Murphy, JR

Toxins (Basel) 2011
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
protein transmembrane transporter activity of DT:HBEGF:CD9 [endocytic vesicle membrane]
Physical Entity
DT:HBEGF:CD9 [endocytic vesicle membrane]
Activity
protein transmembrane transporter activity (0008320)
This event is regulated
Positively by
Disease
Name Identifier Synonyms
diphtheria 11405 corynebacterium infection
Authored
D'Eustachio, P  (2014-03-04)
Reviewed
Liu, S  (2014-11-18)
Created
D'Eustachio, P  (2014-03-02)