Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure
James H. Felce,
Sarah L. Latty,
Rachel G. Knox,
Susan R. Mattick,
Yuan Lui,
Steven F. Lee,
David Klenerman,
Simon J. Davis
Affiliations
James H. Felce
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Sarah L. Latty
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Rachel G. Knox
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Susan R. Mattick
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Yuan Lui
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
Steven F. Lee
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
David Klenerman
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Simon J. Davis
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK
The organization of Rhodopsin-family G protein-coupled receptors (GPCRs) at the cell surface is controversial. Support both for and against the existence of dimers has been obtained in studies of mostly individual receptors. Here, we use a large-scale comparative study to examine the stoichiometric signatures of 60 receptors expressed by a single human cell line. Using bioluminescence resonance energy transfer- and single-molecule microscopy-based assays, we found that a relatively small fraction of Rhodopsin-family GPCRs behaved as dimers and that these receptors otherwise appear to be monomeric. Overall, the analysis predicted that fewer than 20% of ∼700 Rhodopsin-family receptors form dimers. The clustered distribution of the dimers in our sample and a striking correlation between receptor organization and GPCR family size that we also uncover each suggest that receptor stoichiometry might have profoundly influenced GPCR expansion and diversification.
