Glycan-dependent cell adhesion mechanism of Tc toxins

Roderer, Daniel; Bröcker, Felix; Sitsel, Oleg; Kaplonek, Paulina; Leidreiter, Franziska; Seeberger, Peter H.; Raunser, Stefan

doi:10.1038/s41467-020-16536-7

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Glycan-dependent cell adhesion mechanism of Tc toxins

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Bröcker, Felix
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Kaplonek, Paulina
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Seeberger, Peter H.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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引用

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

引用: https://hdl.handle.net/21.11116/0000-0006-866C-A

要旨

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.