EMD-10797
Xenorhabdus nematophila XptA1 in complex with porcine mucosa heparin
EMD-10797
Single-particle3.7 Å

Map released: 08/07/2020
Last modified: 22/05/2024
Sample Organism:
Xenorhabdus nematophila
Sample: Xenorhabdus nematophila XptA1 pentamer in complex with porcine mucosa heparin
Fitted models: 6yey (Avg. Q-score: 0.434)
Deposition Authors: Roderer D
,
Broecker F,
Sitsel O
,
Kaplonek P,
Leidreiter F,
Seeberger PH,
Raunser S
Sample: Xenorhabdus nematophila XptA1 pentamer in complex with porcine mucosa heparin
Fitted models: 6yey (Avg. Q-score: 0.434)
Deposition Authors: Roderer D



Glycan-dependent cell adhesion mechanism of Tc toxins.
Roderer D
,
Brocker F,
Sitsel O
,
Kaplonek P,
Leidreiter F,
Seeberger PH,
Raunser S
(2020) Nat Commun , 11 , 2694 - 2694



(2020) Nat Commun , 11 , 2694 - 2694
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.
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.