Vacuolating cytotoxin precursor, VacA of 1287 aas that forms a hexameric pore in the membranes of target cells after processing (Pyburn et al. 2016).  The 88 kDa secreted VacA protein, composed of an N-terminal p33 domain and a C-terminal p55 domain, assembles first into water-soluble oligomers before inserting into membranes.  Details for the insertion process are known (Pyburn et al. 2016).  The biology of VacAs has been reviewed (Foegeding et al. 2016). VacA preferentially associates with lipid rafts, and the affinity of VacA for rafts is independent of its capacity to oligomerize or form membrane channels (Raghunathan et al. 2018).  Cryoelectron microscopy has been used to resolve 10 structures of VacA assemblies, including monolayer (hexamer and heptamer) and bilayer (dodecamer, tridecamer, and tetradecamer) oligomers (Zhang et al. 2019). The models of the 88-kDa full-length VacA protomer derived from the near-atomic resolution maps are highly conserved among different oligomers and show a continuous right-handed beta-helix made up of two domains with extensive domain-domain interactions. The specific interactions between adjacent protomers in the same layer stabilizing the oligomers are well resolved. For double-layer oligomers, short- and/or long-range hydrophobic interactions between protomers across the two layers were found. These structures and other previous observations led to a mechanistic model wherein VacA hexamer correspond to the prepore-forming state, and the N-terminal region of VacA, responsible for the membrane insertion would undergo a large conformational change to bring the hydrophobic transmembrane region to the center of the oligomer for the membrane channel formation (Zhang et al. 2019). VacA enters cells, localizes to mitochondria, and induces mitochondrial membrane permeability changes due to toxin channel activity (Willhite and Blanke 2004).