The stoichiometric ‘signature’ of Rhodopsin-family G protein-coupled receptors

Abstract

AbstractWhether Rhodopsin-family G protein-coupled receptors (GPCRs) form dimers is highly controversial, with much data both for and against emerging from studies of mostly individual receptors. The types of large-scale comparative studies from which a consensus could eventually emerge have not previously been attempted. Here, we sought to determine the stoichiometric “signatures” of 60 GPCRs expressed by a single human cell-line using orthogonal bioluminescence resonance energy transfer-based and single-molecule microscopy assays. We observed that a relatively small fraction of Rhodopsin-family GPCRs behaved as dimers and that these receptors otherwise appeared to be monomeric. Mapped onto the entire family the analysis predicted that fewer than 20% of the ~700 Rhodopsin- family receptors form dimers. The clustered distribution of Rhodopsin-family dimers, and a striking correlation between receptor stoichiometry and GPCR family-size that we also identified, suggested that evolution has tended to favor the lineage expansion of monomers rather than dimers.One Sentence SummaryAnalysis of 71 GPCRs from a single cell reveals the strong tendency of Rhodopsin-family receptors to exist as monomers rather than form dimers.