1.C.41.2.8
Two component cytotoxin consisting of XaxA of 408 aas and XaxB of 350 aas. Xenorhabdus nematophila, a member of the Enterobacteriaceae, kills many species of insects by strongly depressing the immune system and colonizing the entire body. The peptide cytotoxin, XaxAB, has been purified from X. nematophila broth, and the cytolytic effect on insect immunocytes and the hemolytic effect on mammalian red blood cells have been described (Vigneux et al. 2007). This toxin, Xenorhabdus alpha-xenorhabdolysin (Xax), triggers apoptosis in both insect and mammalian cells. Vigneux et al. 2007 also cloned and sequenced xaxAB, and showed that hemolytic activity was observed only if the two proteins were added in the appropriate order. The membrane inserted complex forms a 1-1.3 MDa large pore complexes to perforate the host cell membrane. Schubert et al. 2018 reported the cryo-EM structure of the XaxAB pore complex and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12-15 subunit containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix, are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. A novel structural model for the mechanism of Xax intoxication was proposed (Schubert et al. 2018). Kopanja et al. 2018 determined the influence of an ostreolysin A/pleurotolysin B complex (OlyA/PlyB) on the morphology of murine neuronal NG108-15 cells. The 3D structure at 4 Å resolution has been solved (PDB# 6GY6; Gupta et al. 2023).