AChRs: five-fold symmetry and the ε-subunit

Abstract

A combination of molecular genetic, electrophysiological, and structural techniques is starting to provide a view of the acetylcholine receptor (AChR) channel that is more detailed and precise than could be imagined just a few years ago. The latest information reveals that, even though this channel is constructed from four distinct peptides specified by four separate genes, the overall structure is a highly symmetric one generally similar to the well-studied gap junction channel. These new observations suggest that many types of channels may be constructed with similar symmetry principles, and that this symmetry implies gating mechanisms that make use of corresponding conformational changes in the participating subunits or domains. Although the separate subunits have the same general shape, they are only partially interchangeable, and a start has been made on discovering the structural basis for functional interchangeability. Certainly, the techniques are at hand now 1 for discovering the role of symmetry in channel function, and the significance of departures from complete symmetry.