| abstract |
toxin effector region membrane localization domain. This MLD domain functions as a membrane-targeting domain for toxin effectors such as the Rho-inactivation domain of Vibrio MARTX, Pasteurella mitogenic toxin (PMT), where it has been termed PMT C1 domain, and clostridial glycosylating cytotoxins including Clostridium difficile toxins A (TcdA) and B (TcdB), Clostridium novyi alpha-toxin (TcnA), and Clostridium sordellii lethal toxin (TcsL). During infection, the C. difficile homologous exotoxins, TcdA and TcdB, target and disrupt the colonic epithelium, leading to diarrhea and colitis. They disrupt host cell function through a multistep process involving receptor binding, endocytosis, low pH-induced pore formation, and the translocation and delivery of a C-terminal glucosyltransferase domain (GTD) that inactivates host GTPases. Their N-terminal MLD domains confer membrane localization of adjacent effector domains via the 4-helix-bundle motif. |