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Journal Article

Glycan-dependent cell adhesion mechanism of Tc toxins

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Roderer, D., Bröcker, F., Sitsel, O., Kaplonek, P., Leidreiter, F., Seeberger, P. H., et al. (2020). Glycan-dependent cell adhesion mechanism of Tc toxins. Nature Communications, 11: 2694, pp. 1-13. doi:10.1038/s41467-020-16536-7.


Cite as: http://hdl.handle.net/21.11116/0000-0006-808B-C
Abstract
Toxin complex (Tc) toxins are virulence factors of pathogenic bacteria. Tcs are composed of three subunits: TcA, TcB and TcC. TcA facilitates receptor–toxin interaction and membrane permeation, TcB and TcC form a toxin-encapsulating cocoon. While the mechanisms of holotoxin assembly and pore formation have been described, little is known about receptor binding of TcAs. Here, we identify heparins/heparan sulfates and Lewis antigens as receptors for different TcAs from insect and human pathogens. Glycan array screening reveals that all tested TcAs bind negatively charged heparins. Cryo-EM structures of Morganella morganii TcdA4 and Xenorhabdus nematophila XptA1 reveal that heparins/heparan sulfates unexpectedly bind to different regions of the shell domain, including receptor-binding domains. In addition, Photorhabdus luminescens TcdA1 binds to Lewis antigens with micromolar affinity. Here, the glycan interacts with the receptor-binding domain D of the toxin. Our results suggest a glycan dependent association mechanism of Tc toxins on the host cell surface.