Tc toxins from pathogenic bacteria use a special syringe-like mechanism to 
perforate the host cell membrane and inject a deadly enzyme into the host 
cytosol. The molecular mechanism of this unusual injection system is poorly 
understood. Using electron cryomicroscopy, we determined the structure of TcdA1 
from Photorhabdus luminescens embedded in lipid nanodiscs. In our structure, 
compared with the previous structure of TcdA1 in the prepore state, the 
transmembrane helices rearrange in the membrane and open the initially closed 
pore. However, the helices do not span the complete membrane; instead, the loops 
connecting the helices form the rim of the funnel. Lipid head groups reach into 
the space between the loops and consequently stabilize the pore conformation. 
The linker domain is folded and packed into a pocket formed by the other domains 
of the toxin, thereby considerably contributing to stabilization of the pore 
state.