title: On the interaction of Clostridium perfringens enterotoxin with claudins.
abstract: Clostridium perfringens causes one of the most common foodborne illnesses, which is largely mediated by the Clostridium perfringens enterotoxin (CPE). The toxin consists of two functional domains. The N-terminal region mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins. Claudin-3 and claudin-4 have been shown to be receptors for CPE with very high affinity. The toxin binds with weak affinity to claudin-1 and -2 but contribution of these weak binding claudins to CPE-mediated disease is questionable. cCPE is not cytotoxic, however, it is a potent modulator of tight junctions. This review describes recent progress in the molecular characterization of the cCPE-claudin interaction using mutagenesis, in vitro binding assays and permeation studies. The results promote the development of recombinant cCPE-proteins and CPE-based peptidomimetics to modulate tight junctions for improved drug delivery or to treat tumors overexpressing claudins.
authors: Leibniz-Institut für molekulare Pharmakologie, Robert-Rössle-Str.10, 13125 Berlin, Germany. veshnyakova@fmp-berlin.de
authors: Anna
authors: A
authors: Veshnyakova
authors: Jonas
authors: J
authors: Protze
authors: Jan
authors: J
authors: Rossa
authors: Ingolf E
authors: IE
authors: Blasig
authors: Gerd
authors: G
authors: Krause
authors: Joerg
authors: J
authors: Piontek
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D057167:Claudins / Q000378:metabolism*; D003016:Clostridium perfringens; D004768:Enterotoxins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D057167:Claudins; D004768:Enterotoxins; D011994:Recombinant Proteins; C035598:enterotoxin, Clostridium