Glycan-dependent cell adhesion mechanism of Tc toxins.
Animals
Bacterial Toxins
/ chemistry
Binding Sites
Cell Adhesion
/ drug effects
Cell Membrane
/ drug effects
HEK293 Cells
Heparin
/ chemistry
Humans
Insecta
/ microbiology
Lewis X Antigen
/ chemistry
Models, Molecular
Molecular Docking Simulation
Morganella morganii
/ pathogenicity
Photorhabdus
/ pathogenicity
Polysaccharides
/ chemistry
Xenorhabdus
/ pathogenicity
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
10
12
2019
accepted:
11
05
2020
entrez:
3
6
2020
pubmed:
3
6
2020
medline:
25
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32483155
doi: 10.1038/s41467-020-16536-7
pii: 10.1038/s41467-020-16536-7
pmc: PMC7264150
doi:
Substances chimiques
Bacterial Toxins
0
Lewis X Antigen
0
Polysaccharides
0
Heparin
9005-49-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2694Références
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