Fig. 1. The structural features of ligand-gated ion channel family receptors. A  shows a schematic of the primary sequence for all subunits; the amino-terminus is at the left. The amino-terminal extracellular domain contains the loops contributing to the transmitter binding site, A through F. Three transmembrane domains, TM1, TM2, and TM3, then lead to the major cytoplasmic domain, also known as the TM3-TM4 loop. The subunit then ends with a fourth transmembrane domain and a short carboxyl-terminal domain. B  shows the folding of a single subunit with respect to the cell membrane. The orange oval  shows the approximate location of the transmitter-binding site. The second transmembrane domain (shown in red ) forms the major portion of the ion channel lining. C  shows the arrangement of subunits in the assembled pentameric receptor, viewed from the extracellular side. The hatched circle  in the middle represents the ion channel. The subunits contributing the primary (positive or +) side of the transmitter-binding site are identified as 1^o(gold circles ), whereas the subunits contributing the complementary side are identified as 2^oand are blue . The locations of transmitter-binding sites are indicated by the red diamonds . The fifth or structural subunit (indicated by X; unfilled circle ) does not contribute to a transmitter-binding site but impacts the functional properties of the overall receptor and may contain sites for pharmacological agents. D  shows an image of a three-subunit concatemer. The blue-hatched segment  is the signal sequence of the first subunit, the black segments  are the “linkers” connecting subunits, and the subunits are schematized in red  with membrane-spanning regions cross-hatched. The signal sequence is cleaved from the mature subunit and is not present in the assembled receptor. E  shows a simplified version of a two-subunit concatemer in the membrane; other subunits are omitted for clarity. The cylinders outline the subunits, the red lines  indicate the general course of the peptide in the subunit, and the black line  indicates a hypothetical path for a linker to connect the subunits.