Pore dimensions of aSlo1 channels accommodate large blockers. (A) Pore radius for liganded and metal free Aplysia Slo1 structures along with the open KvChim structure are compared. Residue numbering corresponds to Aplysia on left and mammalian Slo1 on right. Shaded area corresponds approximately to the lipid bilayer dimensions. (B, D, and F) The open KvChim pore is compared with the closed KscA pore. The open KvChim structure is used here because it contains an attached VSD domain. (C) bbTBA can be accommodated deep in the inner cavity in both liganded and metal-free aSlo1 structures. Here and in D, the bbTBA orientation was constrained to place the quaternary group as close as possible to the observed position of TEA occupancy in KcsA (Lenaeus et al., 2005). (D) bbTBA is unlikely to penetrate deeply into an open KvChim pore. (E) An α-helical conformation of the 10 N-terminal residues of the Shaker extended ball peptide can be docked in both the liganded and metal-free aSlo1 structures. Blocker orientation was chosen to allow deepest penetration. (F) The Shaker EBP in a compact helical structure would be unlikely to penetrate deeply into a KvChim-like pore, without adopting a random coil.