Model of the acetylcholine receptor (AChR) showing a transverse section (top panel), a top view (middle panel) and the alpha-subunit in the membrane (bottom panel). In the top panel, the extracellular and smaller intracellular vestibules that surround the transmembrane ion pore are lined with negative charges. The main immunogenic region (MIR) of the AChR is located at the top of the extracellular portion of the AChR. The transmembrane pore is formed by the M1 and M2 segments of each subunit. The narrowing of the transmembrane ion pore results from bending of the M2 segment. The narrowest part of the pore is the selectivity filter. In the middle panel, "ACh" indicates the alpha/delta and alpha/epsilon or alpha/gamma agonist-binding sites. The lower panel shows the arrangement of the alpha-subunit within the membrane. The subunits are homologous. Each subunit has four transmembrane segments, called M1-M4. The dots on the N-terminal extracellular segment represent the location of amino acids that contribute to the alpha-subunit agonist binding site. The binding site amino acids of the alpha-subunit are tyrosines at alpha 93, alpha 190, and alpha 198, cysteines at alpha 192 and alpha 193, and tryptophan at alpha 149. The MIR is alpha 61 to alpha 76. Note that both the N-terminal and C-terminal portions of the subunit are extracellular. The configurations of the other subunits are similar to that of the alpha-subunit.