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TitleGlycan-dependent cell adhesion mechanism of Tc toxins.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 2694, Year 2020
Publish dateJun 1, 2020
AuthorsDaniel Roderer / Felix Bröcker / Oleg Sitsel / Paulina Kaplonek / Franziska Leidreiter / Peter H Seeberger / Stefan Raunser /
PubMed AbstractToxin 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 ...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.
External linksNat Commun / PubMed:32483155 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 5.0 Å
Structure data

EMDB-10794:
Photorhabdus luminescens TcdA1 in complex with BSA-Lewis X
Method: EM (single particle) / Resolution: 5.0 Å

10796

6yew

EMDB-10796, PDB-6yew:
Morganella morganii TcdA4 in complex with porcine mucosa heparin
Method: EM (single particle) / Resolution: 3.2 Å

10797

6yey

EMDB-10797, PDB-6yey:
Xenorhabdus nematophila XptA1 in complex with porcine mucosa heparin
Method: EM (single particle) / Resolution: 3.7 Å

Source
  • Photorhabdus luminescens (bacteria)
  • Bos taurus (cattle)
  • morganella morganii (bacteria)
  • xenorhabdus nematophila (bacteria)
KeywordsTOXIN / complex / glycan

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