Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB

Nat Commun. 2018 May 4;9(1):1806. doi: 10.1038/s41467-018-04139-2.


Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound 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 two-component 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / metabolism
  • Cryoelectron Microscopy
  • Humans
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Multiprotein Complexes / ultrastructure
  • Pore Forming Cytotoxic Proteins / chemistry*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Pore Forming Cytotoxic Proteins / ultrastructure
  • Protein Conformation, alpha-Helical*
  • Protein Multimerization*
  • Virulence
  • Yersinia / metabolism
  • Yersinia / pathogenicity
  • Yersinia Infections / microbiology


  • Bacterial Toxins
  • Multiprotein Complexes
  • Pore Forming Cytotoxic Proteins