article published yes Bastian Bräuning author Eva Bertosin author Florian M Praetorius author dfec9381-4341-11ee-8fd8-faa02bba7d62 Christian Ihling author Alexandra Schatt author Agnes Adler author Klaus Richter author Andrea Sinz author Hendrik Dietz author Michael Groll author 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. Springer Nature2018 eng General Physics and AstronomyGeneral BiochemistryGenetics and Molecular BiologyGeneral ChemistryMultidisciplinary 2041-1723 2972860610.1038/s41467-018-04139-2 9 yes Bräuning, Bastian, et al. “Structure and Mechanism of the Two-Component α-Helical Pore-Forming Toxin YaxAB.” <i>Nature Communications</i>, vol. 9, 1806, Springer Nature, 2018, doi:<a href="https://doi.org/10.1038/s41467-018-04139-2">10.1038/s41467-018-04139-2</a>. Bräuning B, Bertosin E, Praetorius FM, Ihling C, Schatt A, Adler A, Richter K, Sinz A, Dietz H, Groll M. 2018. Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB. Nature Communications. 9, 1806. Bräuning, B., Bertosin, E., Praetorius, F. M., Ihling, C., Schatt, A., Adler, A., … Groll, M. (2018). Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB. <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-018-04139-2">https://doi.org/10.1038/s41467-018-04139-2</a> Bräuning, Bastian, Eva Bertosin, Florian M Praetorius, Christian Ihling, Alexandra Schatt, Agnes Adler, Klaus Richter, Andrea Sinz, Hendrik Dietz, and Michael Groll. “Structure and Mechanism of the Two-Component α-Helical Pore-Forming Toxin YaxAB.” <i>Nature Communications</i>. Springer Nature, 2018. <a href="https://doi.org/10.1038/s41467-018-04139-2">https://doi.org/10.1038/s41467-018-04139-2</a>. B. Bräuning <i>et al.</i>, “Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB,” <i>Nature Communications</i>, vol. 9. Springer Nature, 2018. Bräuning B, Bertosin E, Praetorius FM, et al. Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB. <i>Nature Communications</i>. 2018;9. doi:<a href="https://doi.org/10.1038/s41467-018-04139-2">10.1038/s41467-018-04139-2</a> B. Bräuning, E. Bertosin, F.M. Praetorius, C. Ihling, A. Schatt, A. Adler, K. Richter, A. Sinz, H. Dietz, M. Groll, Nature Communications 9 (2018). 142842023-09-06T12:07:33Z2023-11-07T11:46:12Z