Receptor-Binding and Uptake of Binary Actin-ADP-Ribosylating Toxins

Abstract

Binary actin-ADP-ribosylating toxins (e.g., Clostridium botulinum C2 toxin or Clostridium perfringens iota toxin ) consist of two separate proteins: An ADP-ribosyltransferase, which modifies actin thereby inhibiting actin polymerization, and a binding component that forms heptamers after proteolytic activation. While C2 toxin interacts with carbohydrate structures on host cells, the group of iota-like toxins binds to lipolysis-stimulated lipoprotein receptor (LSR). Here, we review LSR and discuss the role and function of LSR in interaction of iota-like toxins with host cells.

AFM Imaging Suggests Receptor-Free Penetration of Lipid Bilayers by Toxins

“…Many exotoxins have been found to be intercellularly active “AB toxins”, composed of a “B” part responsible for binding to the target membrane (B for binding) that then translocates the “A” part (A for enzymatic action) through the membrane. The mechanism of this translocation is much debated. , Common examples are Anthrax toxin or Clostridium botulinum C2-Toxin. − …”

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

“…Acidification of EE triggers the insertion of oligomers into the EE membrane and the formation of functional pores allowing the transfer of the enzymatic components into the cytosol. Translocation of the enzymatic component also requires cytosolic chaperones [ 158 , 231 , 232 , 233 , 234 ]. The intracellular activity of clostridial and related Bacillus binary toxins consists of monoADP-ribosylation of actin monomers at Arg177 that is located in the interface between actin monomers.…”

Role of toxins in Clostridium difficile pathogenicity

“…Особенность данного вещества заключается в том, что он продуцируется не в виде одной белковой цепи, как TcdA или TcdB, а в виде двух индивидуальных полипептидов -компонентов А (CDT-A) и В (CDT-B) и относится, таким образом, к группе бинарных токсинов (Рис. 3) [45].…”

“…В частности, токсины C. diffi cile широко используются в исследованиях, посвященных изучению процессов онкотрансформации и метастазирования раковых клеток [76,77]. Важная область использования знаний о токсических молекулах -это разработка способов внутриклеточной доставки биологически-активных веществ [43,45,78]. Последнее направление может привести к разработке новых лекарственных средств, направленных на терапевтическую модуляцию разнообразных внутриклеточных процессов, в том числе, развитие злокачественных опухолей человека.…”