Vacuolating cytotoxin A p33–p55 intramolecular interface (VacA p33–p55 interface)

Vacuolating cytotoxin A (VacA) is a major virulence factor secreted by the bacterium Helicobacter pylori, which is strongly associated with the development of peptic ulcers and gastric cancer (Cover & Blanke, 2005, Nat Rev Microbiol). The mature 88 kDa toxin is composed of two primary domains, p33 and p55, which are joined by a flexible linker; the interaction between these domains at the p33–p55 intramolecular interface is essential for the toxin's structural stability and its ability to form functional oligomers (Gangwer et al., 2007, PNAS). Once secreted, VacA monomers assemble into large, wheel-like oligomeric complexes that insert into host cell membranes to form anion-selective channels. These channels disrupt endosomal trafficking, leading to the characteristic formation of large cytoplasmic vacuoles and the induction of mitochondrial-mediated apoptosis (Foegeding et al., 2016, MBio). The p33–p55 interface represents a critical therapeutic target because its disruption prevents the transition from an inactive monomer to a cytotoxic oligomer. Small molecules or peptides designed to bind this interface can effectively neutralize the toxin's activity, offering a potential non-antibiotic strategy to mitigate H. pylori-induced gastric damage and reduce the risk of oncogenesis (Iv et al., 2014, Proc Natl Acad Sci U S A).

Other names

VacA p33-p55 domain interfaceVacuolating cytotoxin A domain-domain interfaceH. pylori VacA p33-p55 junctionVacA p33/p55 interface

Disruption of the p33–p55 domain interaction to prevent toxin oligomerization, membrane insertion, and subsequent pore-forming activity.