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Comment
. 2020 Sep 19;5(1):206.
doi: 10.1038/s41392-020-00307-3.

Semaphorins or Frizzled -it is the receptor that direct the action of clostridial glucosylating toxins

Klaus Aktories  1
Affiliations
Comment

Semaphorins or Frizzled -it is the receptor that direct the action of clostridial glucosylating toxins

Klaus Aktories. Signal Transduct Target Ther. .
No abstract available

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Figures

Fig. 1
Fig. 1
Interaction of TcsL with semaphorins. a Schemes of the structures of TcsL and TcdB. Both toxins consist of the glucosyltransferase domain (GTD), the auto-protease domain (APD), the delivery and binding domain (D/B), and the C-terminal CROP (combined repetitive oligopeptide) domain. For Cryo-EM studies of the interaction of TcsL with the extracellular domain of Semaphorin 6A, a TcsL region located in D/B (residues 1285–1804) was used. Exactly this region was employed for the crystal structure analysis of TcdB in complex with the cysteine-rich domain (CRD) of Frizzled 2 (FZD2). The interaction of both toxins with their specific receptors is almost identical. b Scheme of the action of TcsL. TcsL binds to the extracellular domain (ECD) of Sema6A and 6B (which form dimers) within the D/B domain. Then, the toxin receptor complex is endocytosed. At low pH of endosomes, the toxin inserts into endosomal membranes and translocates the GTD and APD domains into the cytosol. Here, APD is activated by inositol hexakisphosphate (InsP6) and releases GTD. TcsL GTD glucosylates Rac and Ras proteins (and probably other related GTPases), thereby causing destruction of the cytoskeleton and cell death. The interaction of TcdB with its major receptor Frizzled (FZD1, 2, 7) is indicated. Further uptake steps of TcdB (probably similar to TcsL) are not shown
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References

    1. Lee H, et al. Recognition of semaphorin proteins by P. sordellii lethal toxin reveals principles of receptor specificity in clostridial toxins. Cell. 2020;182:345–356.e16. doi: 10.1016/j.cell.2020.06.005. - DOI - PMC - PubMed
    1. Aktories K, Schwan C, Jank T. Clostridium difficile toxin biology. Annu. Rev. Microbiol. 2017;71:281–307. doi: 10.1146/annurev-micro-090816-093458. - DOI - PubMed
    1. Geny B, et al. Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability. Am. J. Pathol. 2007;170:1003–1017. doi: 10.2353/ajpath.2007.060583. - DOI - PMC - PubMed
    1. Tian S, et al. Genome-wide CRISPR screen identifies semaphorin 6A and 6B as receptors for Paeniclostridium sordellii toxin TcsL. Cell Host Microbe. 2020;27:782–792.e787. doi: 10.1016/j.chom.2020.03.007. - DOI - PMC - PubMed
    1. Chen P, et al. Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B. Science. 2018;360:664–669. doi: 10.1126/science.aar1999. - DOI - PMC - PubMed