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Uptake and function of diphtheria toxin
Stable Identifier
R-HSA-5336415
DOI
10.3180/REACT_268571.1
Type
Pathway
Species
Homo sapiens
Related Species
Corynephage beta
ReviewStatus
5/5
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Uptake and actions of bacterial toxins (Homo sapiens)
Uptake and function of diphtheria toxin (Homo sapiens)
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Diphtheria is a serious, often fatal human disease associated with damage to many tissues. Bacteria in infected individuals, however, are typically confined to the lining of the throat or to a skin lesion; systemic effects are due to the secretion of an exotoxin encoded by a lysogenic bacteriophage. The toxin is encoded as a single polypeptide but is cleaved by host furin-like proteases to yield an aminoterminal fragment A and a carboxyterminal fragment B, linked by a disulfide bond. Toxin cleavage can occur when it first contacts the target cell surface, as annotated here, or as late as the point at which fragment A is released into the cytosol. Fragment B mediates toxin uptake into target cell endocytic vesicles, where acidification promotes a conformational change enabling fragment B to form a channel in the vesicle membrane through which fragment A is extruded into the target cell cytosol. Cleavage of the inter-fragment disulfide bond frees DT fragment A, which catalyzes ADP ribosylation of the translation elongation factor 2 (EEF2) in a target cell, thereby blocking protein synthesis. Neither fragment is toxic to human cells by itself (Collier 1975; Pappenheim 1977; 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
20040
Diphtheria toxin
Pappenheimer, AM
Annu. Rev. Biochem.
1977
164179
Diphtheria toxin: mode of action and structure
Collier, RJ
Bacteriol Rev
1975
Participants
Events
DT A:B binds HBEGF and CD9 on the target cell surface
(Homo sapiens)
Clathrin-mediated endocytosis of DT:HBEGF:CD9
(Homo sapiens)
DT:HBEGF:CD9 is transported from clathrin-coated vesicle to endosome
(Homo sapiens)
DT fragment B transports DT fragment A from target cell endosome membrane
(Homo sapiens)
DT fragment A ADP-ribosylates target cell EEF
(Homo sapiens)
Participates
as an event of
Uptake and actions of bacterial toxins (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)
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