Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure

Publication date: 12 September 2017
Source:Cell Reports, Volume 20, Issue 11
Author(s): James H. Felce, Sarah L. Latty, Rachel G. Knox, Susan R. Mattick, Yuan Lui, Steven F. Lee, David Klenerman, Simon J. Davis
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.

Graphical abstract

Teaser

The quaternary organization of Rhodopsin-family GPCRs is controversial. Felce et al. show that 60 receptors are mostly monomeric. They propose a simple explanation for the remarkable asymmetry in GPCR family structure, i.e., that it is underpinned by the lineage expansion of monomers rather than dimers.


http://ift.tt/2w8e0AK