Glycan-dependent cell adhesion mechanism of Tc toxins
| Autor: | Paulina Kaplonek, Stefan Raunser, Peter H. Seeberger, Daniel Roderer, Oleg Sitsel, Felix Bröcker, F. Leidreiter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Models Molecular Glycan Insecta Science Bacterial Toxins General Physics and Astronomy Virulence Lewis X Antigen General Biochemistry Genetics and Molecular Biology Article Xenorhabdus 03 medical and health sciences Cryoelectron microscopy Polysaccharides Photorhabdus luminescens Cell Adhesion Animals Humans Binding site Receptor Cell adhesion lcsh:Science Host cell surface Morganella morganii Multidisciplinary Binding Sites 030102 biochemistry & molecular biology biology Chemistry Heparin HEK 293 cells Cell Membrane General Chemistry biology.organism_classification Molecular Docking Simulation 030104 developmental biology HEK293 Cells Biochemistry biology.protein lcsh:Q Pathogens Structural biology Photorhabdus |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Although Tc toxins are a major class of bacterial toxin translocation systems, little is known about their receptor binding. Here, the authors identify heparins/heparan sulfates and Lewis antigens as receptors for different Tc toxins, determine cryo-EM structures of three toxin-glycan complexes and propose a two-step cell adhesion mechanism for Tc toxins. |
| Databáze: | OpenAIRE |
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