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TitleMechanism of Tc toxin action revealed in molecular detail.
Journal, issue, pagesNature, Vol. 508, Issue 7494, Page 61-65, Year 2014
Publish dateApr 3, 2014
AuthorsDominic Meusch / Christos Gatsogiannis / Rouslan G Efremov / Alexander E Lang / Oliver Hofnagel / Ingrid R Vetter / Klaus Aktories / Stefan Raunser /
PubMed AbstractTripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly ...Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood. Here we report the first, to our knowledge, high-resolution structures of a TcA subunit in its prepore and pore state and of a complete 1.7 megadalton Tc complex. The structures reveal that, in addition to a translocation channel, TcA forms four receptor-binding sites and a neuraminidase-like region, which are important for its host specificity. pH-induced opening of the shell releases an entropic spring that drives the injection of the TcA channel into the membrane. Binding of TcB/TcC to TcA opens a gate formed by a six-bladed β-propeller and results in a continuous protein translocation channel, whose architecture and properties suggest a novel mode of protein unfolding and translocation. Our results allow us to understand key steps of infections involving Tc toxins at the molecular level.
External linksNature / PubMed:24572368
MethodsEM (single particle) / X-ray diffraction
Resolution2.17 - 9.0 Å
Structure data

EMDB-2551:
Electron cryo-microscopy of the PTC3 holotoxin complex (TcdA1, TcdB2, TccC3) in prepore state
Method: EM (single particle) / Resolution: 9.0 Å

EMDB-2552:
Electron cryo-microscopy of TcdA1 in pore state.
Method: EM (single particle) / Resolution: 9.0 Å

PDB-4o9x:
Crystal Structure of TcdB2-TccC3
Method: X-RAY DIFFRACTION / Resolution: 2.17 Å

PDB-4o9y:
Crystal Structure of TcdA1
Method: X-RAY DIFFRACTION / Resolution: 3.502 Å

Chemicals

ChemComp-HG:
Unknown entry / Mercury (element)

ChemComp-HOH:
WATER / Water

Source
  • photorhabdus luminescens (bacteria)
KeywordsTOXIN / beta sheet / cocoon / unfolding / tc toxin / pore-forming / transmembrane

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