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Biochem Biophys Res Commun. 2003 Jan 17;300(3):706-11.

The complete receptor-binding domain of Clostridium difficile toxin A is required for endocytosis.

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Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Albertstr. 25, 79104 Freiberg, Germany.


Clostridium difficile toxin A, the chief pathogenicity factor of the antibiotic-associated pseudomembranous colitis, is an intracellular acting cytotoxin that reaches its targets, the Rho GTPases, after receptor-mediated endocytosis. The C-terminal part, constructed of repetitive peptide elements, is thought to bind to a lot of carbohydrate containing receptor molecules to induce clustering and endocytosis. To study which part of the receptor-binding domain is in charge of addressing toxin A into the target cells, we studied the functional, i.e., endocytosis-inducing, binding of toxin A. By a competition assay between various receptor-binding fragments of toxin A and the holotoxin A we found that the complete receptor-binding domain, encompassing the entire repetitive elements, but not parts of it, is necessary for binding-induced endocytosis. The receptor binding domain itself shows weaker competition with holotoxin A than the fragment consisting of receptor-binding domain plus intermediary part of the toxin. All toxin A fragments that compete with holotoxin A are capable of inducing their own endocytosis. Thus, the entire receptor-binding domain, covering the C-terminal third of the toxin A molecule, is responsible for cell uptake of toxin A and the intermediary part contributes to the correct folding and assembly of the repetitive domains.

[Indexed for MEDLINE]

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