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 == Publication Abstract from PubMed ==
-Clostridium perfringens enterotoxin (CPE) is a major cause of food poisoning and antibiotic-associated diarrhea. Upon its release from C. perfringens spores, CPE binds to its receptor, claudin, at the tight junctions between the epithelial cells of the gut wall and subsequently forms pores in the cell membranes. A number of different complexes between CPE and claudin have been observed, and the process of pore formation has not been fully elucidated. We have determined the three-dimensional structure of the soluble form of CPE in two crystal forms by X-ray crystallography, to a resolution of 2.7 and 4.0 A, respectively, and found that the N-terminal domain shows structural homology with the aerolysin-like beta-pore-forming family of proteins. We show that CPE forms a trimer in both crystal forms and that this trimer is likely to be biologically relevant but is not the active pore form. We use these data to discuss models of pore formation.
+CPE (Clostridium perfringens enterotoxin) is the major virulence determinant for C. perfringens type A food poisoning, the second most common bacterial food-borne illness in the UK and USA. After binding to its receptors, which include particular human claudins, the toxin forms pores in the cell membrane. The mature pore apparently contains a hexamer of CPE, claudin and, possibly, occludin. The combination of high binding specificity with cytotoxicity has resulted in CPE being investigated, with some success, as a targeted cytotoxic agent for oncotherapy. In this paper, we present the X-ray crystallographic structure of CPE in complex with a peptide derived from extracellular loop 2 of a modified, CPE binding Claudin-2, together with high-resolution native and pore-formation mutant structures. Our structure provides the first atomic resolution data on any part of a claudin molecule and reveals that claudin's CPE binding fingerprint (NPLVP), is in a tight turn conformation and binds, as expected, in CPE's C-terminal claudin binding groove. The leucine and valine residues insert into the binding groove while the first residue, asparagine, tethers the peptide via an interaction with CPE's aspartate 225 and the two prolines are required to maintain the tight turn conformation. Understanding the structural basis of the contribution these residues make to binding will aid in engineering CPE to target tumour cells.
-Structure of the Food-Poisoning Clostridium perfringens Enterotoxin Reveals Similarity to the Aerolysin-Like Pore-Forming Toxins.,Briggs DC, Naylor CE, Smedley JG 3rd, Lukoyanova N, Robertson S, Moss DS, McClane BA, Basak AK J Mol Biol. 2011 Oct 14;413(1):138-49. Epub 2011 Aug 3. PMID:21839091<ref>PMID:21839091</ref>
+Structure of a C. perfringens Enterotoxin mutant in Complex with a Modified Claudin-2 Extracellular Loop 2.,Yelland TS, Naylor CE, Bagoban T, Savva CG, Moss DS, McClane BA, Blasig IE, Popoff M, Basak AK J Mol Biol. 2014 Jul 11. pii: S0022-2836(14)00329-5. doi:, 10.1016/j.jmb.2014.07.001. PMID:25020226<ref>PMID:25020226</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>