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
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
DT fragment B transports DT fragment A from target cell endosome membrane
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
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
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
12668662 The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

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

J. Cell Biol. 2003
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein transmembrane transporter activity of DT:HBEGF:CD9 [endocytic vesicle membrane]

Physical Entity
DT:HBEGF:CD9 [endocytic vesicle membrane] (Homo sapiens)
Activity
protein transmembrane transporter activity (GO:0008320)
This event is regulated
Positively by
Regulator
HSP90AA1 [cytosol] (Homo sapiens)
Regulator
H+ [endocytic vesicle lumen]
Regulator
TXNRD1 [cytosol] (Homo sapiens)
Regulator
HSP90AB1 [cytosol] (Homo sapiens)
Disease
Name Identifier Synonyms
diphtheria DOID:11405 corynebacterium infection
Authored
D'Eustachio, P  (2014-03-05)
Reviewed
Liu, S  (2014-11-19)
Created
D'Eustachio, P  (2014-03-03)
Cite Us!