The recently solved three-dimensional structure of amoebapore A, the major pore-forming protein of Entamoeba histolytica, represents the first tertiary structure determined from a parasitic toxin. The implications derived from this solved structure, together with biochemical data, paint a picture of a unique activation mechanism and reveal that a histidine-mediated dimerization of the protein acts as the molecular switch for the formation of oligomeric pores in target cell membranes.