Shrestha Archana, Uzal Francisco A, McClane Bruce A
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
California Animal Health and Food Safety Laboratory, San Bernadino Branch, School of Veterinary Medicine, University of California-Davis, USA.
Anaerobe. 2016 Oct;41:18-26. doi: 10.1016/j.anaerobe.2016.04.011. Epub 2016 Apr 16.
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.
产气荚膜梭菌肠毒素（CPE）因其与几种常见的人类胃肠道疾病有关而具有重要的医学意义。这种35 kDa的单多肽毒素由两个结构域组成：一个参与受体结合的C端结构域和一个参与寡聚化、膜插入和孔形成的N端结构域。CPE的作用始于其与受体的结合，这些受体包括claudin紧密连接蛋白家族的某些成员；结合后的CPE随后形成一系列复合物，其中之一是一个孔，该孔导致钙内流，从而导致宿主细胞死亡。最近的研究表明，CPE与claudin受体的结合涉及CPE C端结构域与claudin受体的第1和第2个细胞外环（ECL-1和ECL-2）之间的相互作用。这种结合特别重要的是ECL-2对接至毒素C端结构域中的一个口袋。对CPE与claudin受体相互作用的这种深入理解正在促进针对CPE介导的胃肠道疾病的受体诱饵疗法、癌症治疗/诊断试剂以及药物递送增强剂的开发。
