Structure of AChR pore domain. (a) Multiple sequence alignment of the M2 region of the AChR subunits. Top: Identical (*) and homologous residues(:); boxed: 9′, 12′, 13′, and 16′ residues. L9′ is conserved except in α5 and β3 where it is a V. V13′ is conserved except in β4 where it is F. L16′ is conserved except in ε and γ where it is an F. (b) Membrane (left, only the β-subunit shown) and synaptic (right) view of the neuromuscular AChR (PDB ID: 7QKO). (c) Helical wheel representation of the pore residues, 8′–18′. The position of the pore is shown by *. 9′, 13′, and 16′ point toward the lumen. (d) HOLE diagram showing pore dimensions of WT AChRs in (left) closed (PDB ID: 7QKO) and (right) open (PDB ID: 7QL6) conformations. Insets: The region between 2′ and 16′. Pore dimension: blue is narrow and red is wide (≥4 Å diameter). Subunits: α orange, β green, δ magenta, and ε cyan; one α-subunit has been removed, for clarity.