Comparison of the three distinct structural states of VCC in a lipid bilayer environment . (A) Top view of the membrane surface–associated VCC shows that the pore is blocked by the lipid layer. (B) Side view of the membrane surface–associated VCC shows part of the β-barrel and faint lipid density (marked orange). Fitting of the heptameric crystal structure shows a markedly small portion of the β-barrel in this cryo-EM structure. (C) Top view of the partially membrane-embedded VCC shows that the pore is blocked by the lipid layer. (D) Side view of the partially membrane-embedded VCC shows the β-barrel embedded in a disordered layer of lipid (marked orange). This class of VCC denotes a structural state where the transmembrane channel is partly bound to the lipid such that there is no perforation on the other end of the membrane. Fitting of the heptameric crystal structure shows visualization of a longer channel compared with the previous structural state. (E) Top view of the completely membrane-embedded VCC shows that a pore is formed in the lipid bilayer. (F) Side view of the completely membrane-embedded VCC shows a long transmembrane β-barrel firmly placed between two relatively ordered layers of lipid (marked orange). Fitting of the heptameric crystal structure shows proper fitting along the length of the oligomer.