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.