Uptake and function of diphtheria toxin

Stable Identifier
R-HSA-5336415
Type
Pathway
Species
Homo sapiens
Related Species
Corynephage beta
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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
20040 Diphtheria toxin

Pappenheimer, AM

Annu. Rev. Biochem. 1977
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
164179 Diphtheria toxin: mode of action and structure

Collier, RJ

Bacteriol Rev 1975
Participants
Participant Of
Disease
Name Identifier Synonyms
diphtheria 11405 corynebacterium infection
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Reviewed
Created