Yousef Sharafi; Seyed Ali Mirhosseini; Jafar Amani
Volume 13, Issue 4 , December 2022, , Pages 501-506
Abstract
Among the 26 human claudin proteins, the food-poisoning bacterium Clostridium perfringens produces an enterotoxin (~ 35.00 kDa) that specifically targets human claudin 4, causing diarrhea by fluid accumulation in the intestinal cavity. The Clostridium perfringens enterotoxin (CPE) C-terminal domain (cCPE ...
Read More
Among the 26 human claudin proteins, the food-poisoning bacterium Clostridium perfringens produces an enterotoxin (~ 35.00 kDa) that specifically targets human claudin 4, causing diarrhea by fluid accumulation in the intestinal cavity. The Clostridium perfringens enterotoxin (CPE) C-terminal domain (cCPE ~ 15.00 kDa) tightly binds to claudin 4 and disrupts the tight junction barriers in the intestines. In this study, we aimed to determine the contribution and type of amino acid interactions involved in association between claudin 4 and the C-terminal CPE. First, the three-dimensional format of claudin 4 was downloaded from RCSB. Then, during 60.00 nanoseconds (nsec), molecular dynamics simulation was conducted using the GROMACS package on CPE of crystallographic structure. The results indicated that the simulations performed well during the simulation times and there were no noticeable problems or artifacts. We found that Coulombic (glycine 317, proline 311 and serine 313) and Lennard-Jones (tyrosine 310, leucine 315, serine 313 and glycine 317) interactions played a significant role in complex stability. This information localized the C-terminal of CPE as a linear sequence sufficient for recognition and binding to the eukaryotic CPE receptor. A detailed description of the dissociation process brings valuable insight into the interaction of the claudin 4-cCPE290-319 complexes, which could help in the future to design more potent drugs.
