YaxAB from Yersinia enterocolitica

[161] Bräuning B., Bertosin E., Praetorius F., Ihling C., Schatt A., Adler A., Richter K., Sinz A., Dietz H., Groll M.
Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB
Nat. Commun., 2018, 9, 1-14, PDF

Pore-forming toxins (PFT) are virulence factors that transform from soluble to membranebound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its twocomponent lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex. Our structures reveal 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. Our results allow for a comparison between pore assemblies belonging to the wider ClyA-like family of α-PFTs, highlighting diverse pore architectures.