1.C.41.2.7
The two component pore-forming toxin (PFT), YaxA-YaxB, where YaxA is 410 aas with 1 central TMS, and YaxB is 344 aas with no TMS. X-ray structures are available (Bräuning et al. 2018). While a yaxAB mutant (ΔyaxAB) is capable of colonizing mice at the same level as the wild type, the mutation slightly delays the course of infection and results in differing pathology in the spleen.  Wagner et al. 2013 found that yaxAB encode a cytotoxin capable of lysing mammalian cells, that both YaxA and YaxB are required for cytotoxic activity, and that the two proteins associate. YaxAB-mediated cell death occurs via osmotic lysis through the formation of distinct membrane pores. In silico tertiary structural analysis identified predicted structural homology between YaxA and proteins in pore-forming toxin complexes from Bacillus cereus (HBL-B) and Escherichia coli (HlyE). Thus, it appears that YaxAB function as virulence factors by inducing cell lysis through the formation of pores in the host cell membrane (Wagner et al. 2013). YaxAB represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens. Bräuning et al. 2018 presented crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex. Their structures revealed a pore predominantly composed of decamers of YaxA-YaxB heterodimers. Both subunits bear membrane-active moieties, but only YaxA is capable of binding to membranes by itself. YaxB can subsequently be recruited to membrane-associated YaxA and induced to present its lytic transmembrane helices. Pore formation can progress by further oligomerization of YaxA-YaxB dimers (Bräuning et al. 2018). The 3D structure is known (PDB# 6GY6 and 6EL1; Gupta et al. 2023). YaxA has a sequence identity of 22% with YaxBm and both proteins have α-helical folds comprising a two-helix coiled-coil stalk and five-helix bundle head domain that is similar to that of ClyA family (Bräuning et al. 2018).