Tc toxins secrete toxic enzymes into host cells using a unique syringe-like 
injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA 
forms the translocation channel and the TcB-TcC heterodimer functions as a 
cocoon that shields the toxic enzyme. Binding of the cocoon to the channel 
triggers opening of the cocoon and translocation of the toxic enzyme into the 
channel. Here we show in atomic detail how the assembly of the three components 
activates the toxin. We find that part of the cocoon completely unfolds and 
refolds into an alternative conformation upon binding. The presence of the toxic 
enzyme inside the cocoon is essential for its subnanomolar binding affinity for 
the TcA subunit. The enzyme passes through a narrow negatively charged 
constriction site inside the cocoon, probably acting as an extruder that 
releases the unfolded protein with its C terminus first into the translocation 
channel.