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Cell Rep. 2017 Sep 12;20(11):2654-2665. doi: 10.1016/j.celrep.2017.08.072.

Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure.

Author information

1
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
2
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
3
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK. Electronic address: dk10012@cam.ac.uk.
4
Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: simon.davis@imm.ox.ac.uk.

Abstract

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.

KEYWORDS:

BRET; G protein-coupled receptors; evolution; single-molecule imaging; stoichiometry

PMID:
28903045
PMCID:
PMC5608970
DOI:
10.1016/j.celrep.2017.08.072
[Indexed for MEDLINE]
Free PMC Article

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