Abstract
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 Xenorhabdus nematophila 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.
Highlights
Pore-forming toxins (PFTs) are soluble proteins produced by bacteria and higher eukaryotes, that spontaneously form pores in biomembranes and act as toxins (Dal Peraro and van der Goot, 2016)
Dependent on their transmembrane region, which is formed either by a-helices or b-strands, PFTs are classified as a-pore-forming toxins (a-PFT) and b-PFTs (Iacovache et al, 2008; Bischofberger et al, 2012)
The five-helix bundle motif has so far only been described for cytolysin A (ClyA) and ClyA-type toxins (Roderer and Glockshuber, 2017)
Summary
Pore-forming toxins (PFTs) are soluble proteins produced by bacteria and higher eukaryotes, that spontaneously form pores in biomembranes and act as toxins (Dal Peraro and van der Goot, 2016). When we incubated soluble monomers of XaxA and XaxB in the absence of detergents at room temperature, we observed the formation of higher oligomers but not of complete pores (Figure 1—figure supplement 3a,b).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
