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Common architecture of Tc toxins from human and insect pathogenic bacteria.

F Leidreiter | D Roderer | D Meusch | C Gatsogiannis | R Benz | S Raunser
Science advances | 2019

Tc toxins use a syringe-like mechanism to penetrate the membrane and translocate toxic enzymes into the host cytosol. They are composed of three components: TcA, TcB, and TcC. Low-resolution structures of TcAs from different bacteria suggest a considerable difference in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures of five TcAs from insect and human pathogens, which show a similar overall composition and domain organization. Essential structural features, including a trefoil protein knot, are present in all TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species to form active chimeric holotoxins. We identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after destabilization of other regions. Our results provide new insights into the architecture and mechanism of the Tc toxin family.

Pubmed ID: 31663026

Research resources used in this publication

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Antibodies used in this publication

None found

Associated grants

  • Agency: European Research Council, International

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