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Glycan-dependent cell adhesion mechanism of Tc toxins
by
Bröcker, Felix
, Roderer, Daniel
, Kaplonek, Paulina
, Raunser, Stefan
, Leidreiter, Franziska
, Seeberger, Peter H.
, Sitsel, Oleg
in
101/28
/ 14/63
/ 49/47
/ 49/61
/ 631/326/421
/ 631/45/535
/ 631/535/1258/1259
/ 82/80
/ 82/83
/ Adhesion
/ Animals
/ Antigens
/ Bacterial Toxins - chemistry
/ Bacterial Toxins - pharmacokinetics
/ Bacterial Toxins - toxicity
/ Binding
/ Binding Sites
/ Cell adhesion
/ Cell adhesion & migration
/ Cell Adhesion - drug effects
/ Cell Adhesion - physiology
/ Cell Membrane - drug effects
/ Cell Membrane - metabolism
/ Cell surface
/ Domains
/ Glycan
/ HEK293 Cells
/ Heparin
/ Heparin - chemistry
/ Heparin - metabolism
/ Humanities and Social Sciences
/ Humans
/ Insecta - microbiology
/ Insects
/ Lewis antigens
/ Lewis X Antigen - chemistry
/ Lewis X Antigen - metabolism
/ Models, Molecular
/ Molecular Docking Simulation
/ Morganella morganii - pathogenicity
/ multidisciplinary
/ Photorhabdus - pathogenicity
/ Polysaccharides - chemistry
/ Polysaccharides - metabolism
/ Pore formation
/ Receptors
/ Science
/ Science (multidisciplinary)
/ Sulfates
/ Toxins
/ Translocation
/ Virulence
/ Virulence factors
/ Xenorhabdus - pathogenicity
2020
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Glycan-dependent cell adhesion mechanism of Tc toxins
by
Bröcker, Felix
, Roderer, Daniel
, Kaplonek, Paulina
, Raunser, Stefan
, Leidreiter, Franziska
, Seeberger, Peter H.
, Sitsel, Oleg
in
101/28
/ 14/63
/ 49/47
/ 49/61
/ 631/326/421
/ 631/45/535
/ 631/535/1258/1259
/ 82/80
/ 82/83
/ Adhesion
/ Animals
/ Antigens
/ Bacterial Toxins - chemistry
/ Bacterial Toxins - pharmacokinetics
/ Bacterial Toxins - toxicity
/ Binding
/ Binding Sites
/ Cell adhesion
/ Cell adhesion & migration
/ Cell Adhesion - drug effects
/ Cell Adhesion - physiology
/ Cell Membrane - drug effects
/ Cell Membrane - metabolism
/ Cell surface
/ Domains
/ Glycan
/ HEK293 Cells
/ Heparin
/ Heparin - chemistry
/ Heparin - metabolism
/ Humanities and Social Sciences
/ Humans
/ Insecta - microbiology
/ Insects
/ Lewis antigens
/ Lewis X Antigen - chemistry
/ Lewis X Antigen - metabolism
/ Models, Molecular
/ Molecular Docking Simulation
/ Morganella morganii - pathogenicity
/ multidisciplinary
/ Photorhabdus - pathogenicity
/ Polysaccharides - chemistry
/ Polysaccharides - metabolism
/ Pore formation
/ Receptors
/ Science
/ Science (multidisciplinary)
/ Sulfates
/ Toxins
/ Translocation
/ Virulence
/ Virulence factors
/ Xenorhabdus - pathogenicity
2020
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Glycan-dependent cell adhesion mechanism of Tc toxins
by
Bröcker, Felix
, Roderer, Daniel
, Kaplonek, Paulina
, Raunser, Stefan
, Leidreiter, Franziska
, Seeberger, Peter H.
, Sitsel, Oleg
in
101/28
/ 14/63
/ 49/47
/ 49/61
/ 631/326/421
/ 631/45/535
/ 631/535/1258/1259
/ 82/80
/ 82/83
/ Adhesion
/ Animals
/ Antigens
/ Bacterial Toxins - chemistry
/ Bacterial Toxins - pharmacokinetics
/ Bacterial Toxins - toxicity
/ Binding
/ Binding Sites
/ Cell adhesion
/ Cell adhesion & migration
/ Cell Adhesion - drug effects
/ Cell Adhesion - physiology
/ Cell Membrane - drug effects
/ Cell Membrane - metabolism
/ Cell surface
/ Domains
/ Glycan
/ HEK293 Cells
/ Heparin
/ Heparin - chemistry
/ Heparin - metabolism
/ Humanities and Social Sciences
/ Humans
/ Insecta - microbiology
/ Insects
/ Lewis antigens
/ Lewis X Antigen - chemistry
/ Lewis X Antigen - metabolism
/ Models, Molecular
/ Molecular Docking Simulation
/ Morganella morganii - pathogenicity
/ multidisciplinary
/ Photorhabdus - pathogenicity
/ Polysaccharides - chemistry
/ Polysaccharides - metabolism
/ Pore formation
/ Receptors
/ Science
/ Science (multidisciplinary)
/ Sulfates
/ Toxins
/ Translocation
/ Virulence
/ Virulence factors
/ Xenorhabdus - pathogenicity
2020
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Journal Article
Glycan-dependent cell adhesion mechanism of Tc toxins
2020
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Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/63
/ 49/47
/ 49/61
/ 82/80
/ 82/83
/ Adhesion
/ Animals
/ Antigens
/ Bacterial Toxins - chemistry
/ Bacterial Toxins - pharmacokinetics
/ Binding
/ Cell Adhesion - drug effects
/ Cell Membrane - drug effects
/ Domains
/ Glycan
/ Heparin
/ Humanities and Social Sciences
/ Humans
/ Insects
/ Lewis X Antigen - metabolism
/ Molecular Docking Simulation
/ Morganella morganii - pathogenicity
/ Photorhabdus - pathogenicity
/ Polysaccharides - metabolism
/ Science
/ Sulfates
/ Toxins
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