title: The interaction of Clostridium perfringens enterotoxin with receptor claudins.
abstract: Clostridium perfringens enterotoxin (CPE) has significant medical importance due to its involvement in several common human gastrointestinal diseases. This 35 kDa single polypeptide toxin consists of two domains: a C-terminal domain involved in receptor binding and an N-terminal domain involved in oligomerization, membrane insertion and pore formation. The action of CPE starts with its binding to receptors, which include certain members of the claudin tight junction protein family; bound CPE then forms a series of complexes, one of which is a pore that causes the calcium influx responsible for host cell death. Recent studies have revealed that CPE binding to claudin receptors involves interactions between the C-terminal CPE domain and both the 1st and 2nd extracellular loops (ECL-1 and ECL-2) of claudin receptors. Of particular importance for this binding is the docking of ECL-2 into a pocket present in the C-terminal domain of the toxin. This increased understanding of CPE interactions with claudin receptors is now fostering the development of receptor decoy therapeutics for CPE-mediated gastrointestinal disease, reagents for cancer therapy/diagnoses and enhancers of drug delivery.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: California Animal Health and Food Safety Laboratory, San Bernadino Branch, School of Veterinary Medicine, University of California-Davis, USA.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Uzal
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: bamcc@pitt.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: McClane
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057167:Claudins / Q000378:metabolism*; D003016:Clostridium perfringens / Q000276:immunology; D004768:Enterotoxins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D060066:Protein Interaction Maps; D015398:Signal Transduction
chemical_list: D057167:Claudins; D004768:Enterotoxins; C035598:enterotoxin, Clostridium
keywords: Claudins; Clostridium perfringens; Enterotoxin; Pore; Receptors