Helicobacter pylori secretes a unique virulence factor, Tipalpha, that enters gastric cells and both stimulates the production of the TNF-alpha and activates the NF-kappaB pathway. The structures of a truncated version of Tipalpha (TipalphaN34) in two crystal forms are presented here. Tipalpha adopts a novel beta(1)alpha(1)alpha(2)beta(2)beta(3)alpha(3)alpha(4) topology that can be described as a combination of three domains. A first region consists in a short flexible extension, a second displays a dodecin-like fold and a third is a helical bundle domain similar to the sterile alpha motif (SAM). Analysis of the oligomerisation states of TipalphaN34 in the crystals and in solution suggests that the disulfide bridges could hold together Tipalpha monomers during their secretion in the gastric environment.