RT Journal Article SR Electronic T1 The stoichiometric ‘signature’ of Rhodopsin-family G protein-coupled receptors JF bioRxiv FD Cold Spring Harbor Laboratory SP 112466 DO 10.1101/112466 A1 James H. Felce A1 Sarah L. Latty A1 Rachel G. Knox A1 Susan R. Mattick A1 Yuan Lui A1 Steven F. Lee A1 David Klenerman A1 Simon J. Davis YR 2017 UL http://biorxiv.org/content/early/2017/03/02/112466.abstract AB Whether 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 Summary Analysis of 71 GPCRs from a single cell reveals the strong tendency of Rhodopsin-family receptors to exist as monomers rather than form dimers.