Investigations of the Structural Properties of the Acetylcholine Receptor and its Polypeptide Subunits from Torpedo Californica

Microsequence analysis of the four polypeptide subunits of the acetylcholine receptor from Torpedo californica electroplax was performed and demonstrated a striking amino acid homology among these four chains. Further sequence analysis of both membrane-bound and Tritonsolubilized, chromatographically purified receptor was used to measure the stoichiometry of the subunits. The values determined for the two preparations of receptor were the same: the ratio of the four subunits (40,000: 50,000:60,000:65,000 daltons) is 2:1:1:1, indicating a value of255,000 daltons for the molecular weight of the receptor, in agreement with experimentally determined values. These results demonstrate that the acetylcholine receptor is a pentamer composed of five subunits, two being identical and the other three being structurally related to them by sequence homology. Genealogical analysis suggests that divergence from a common ancestral gene occurred early in the evolution of the receptor. This shared ancestry argues compellingly that each of the four subunits plays a functional role in the receptor's physiological action.