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Title | Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB. |
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Journal, issue, pages | Nat Commun, Vol. 9, Issue 1, Page 1806, Year 2018 |
Publish date | May 4, 2018 |
Authors | Bastian Bräuning / Eva Bertosin / Florian Praetorius / Christian Ihling / Alexandra Schatt / Agnes Adler / Klaus Richter / Andrea Sinz / Hendrik Dietz / Michael Groll / |
PubMed Abstract | 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, ...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. |
External links | Nat Commun / PubMed:29728606 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.8 - 6.1 Å |
Structure data | PDB-6ek4: PDB-6ek7: PDB-6ek8: |
Chemicals | ChemComp-NA: ChemComp-HOH: ChemComp-MPD: |
Source |
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Keywords | MEMBRANE PROTEIN / pathogens / pore forming toxins / alpha-helical / adventitious membrane protein / Pore-forming toxin / Two-component toxin |