The Ants Go Marching Two by Two: Oligomeric Structure of G-Protein-Coupled Receptors

A number of class C G-protein coupled receptors (GPCRs) have been shown to form dimers in the plasma membrane, and mounting evidence supports the hypothesis that many, if not all, class A rhodopsin-like receptors also form dimers or higher-order oligomers. Evidence for this hypothesis has come from SDS-polyacrylamide gel electrophoresis, coimmunoprecipitation, resonance energy transfer, atomic force microscopy, and cross-linking studies, approaches that are reviewed in this article. Like any method, each has its strengths and limitations, and these must be kept in mind when interpreting the data for oligomerization. Recent experimental evidence supports the hypothesis that class A receptors may exist as higher-order oligomers, or even as arrays, with distinct symmetrical interfaces in both the first and fourth transmembrane segments.