Structural highlights
Publication Abstract from PubMed
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.
Glycan-dependent cell adhesion mechanism of Tc toxins.,Roderer D, Brocker F, Sitsel O, Kaplonek P, Leidreiter F, Seeberger PH, Raunser S Nat Commun. 2020 Jun 1;11(1):2694. doi: 10.1038/s41467-020-16536-7. PMID:32483155[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Roderer D, Bröcker F, Sitsel O, Kaplonek P, Leidreiter F, Seeberger PH, Raunser S. Glycan-dependent cell adhesion mechanism of Tc toxins. Nat Commun. 2020 Jun 1;11(1):2694. PMID:32483155 doi:10.1038/s41467-020-16536-7
