Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure

• Main Authors: James H. Felce, Sarah L. Latty, Rachel G. Knox, Susan R. Mattick, Yuan Lui, Steven F. Lee, David Klenerman, Simon J. Davis
• Format: Article
• Language: English
• Published: Elsevier 2017-09-01
• Series: Cell Reports
• Subjects: G protein-coupled receptors; stoichiometry; BRET; single-molecule imaging; evolution
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717312147

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.