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TitleMembrane insertion of α-xenorhabdolysin in near-atomic detail.
Journal, issue, pagesElife, Vol. 7, Year 2018
Publish dateJul 16, 2018
AuthorsEvelyn Schubert / Ingrid R Vetter / Daniel Prumbaum / Pawel A Penczek / Stefan Raunser /
PubMed Abstractα-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1-1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack ...α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1-1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12-15 subunits containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of Xax intoxication.
External linksElife / PubMed:30010541 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.5 - 4.0 Å
Structure data

0088

6gy6

EMDB-0088, PDB-6gy6:
XaxAB pore complex from Xenorhabdus nematophila
Method: EM (single particle) / Resolution: 4.0 Å

PDB-6gy7:
Crystal structure of XaxB from Xenorhabdus nematophil
Method: X-RAY DIFFRACTION / Resolution: 3.4 Å

PDB-6gy8:
Crystal structure of XaxA from Xenorhabdus nematophila
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • xenorhabdus nematophila atcc 19061 (bacteria)
  • xenorhabdus nematophila (strain atcc 19061 / dsm 3370 / lmg 1036 / ncib 9965 / an6) (bacteria)
KeywordsTOXIN / bacterial toxin / pore forming-toxins

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