Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure
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...
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doaj-ac280b470ad0472b9932a24d661938b72020-11-24T21:12:02ZengElsevierCell Reports2211-12472017-09-0120112654266510.1016/j.celrep.2017.08.072Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family StructureJames H. Felce0Sarah L. Latty1Rachel G. Knox2Susan R. Mattick3Yuan Lui4Steven F. Lee5David Klenerman6Simon J. Davis7Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UKDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UKRadcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UKRadcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UKRadcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UKDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UKDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UKRadcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UKThe 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.http://www.sciencedirect.com/science/article/pii/S2211124717312147G protein-coupled receptorsstoichiometryBRETsingle-molecule imagingevolution |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
James H. Felce Sarah L. Latty Rachel G. Knox Susan R. Mattick Yuan Lui Steven F. Lee David Klenerman Simon J. Davis |
spellingShingle |
James H. Felce Sarah L. Latty Rachel G. Knox Susan R. Mattick Yuan Lui Steven F. Lee David Klenerman Simon J. Davis Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure Cell Reports G protein-coupled receptors stoichiometry BRET single-molecule imaging evolution |
author_facet |
James H. Felce Sarah L. Latty Rachel G. Knox Susan R. Mattick Yuan Lui Steven F. Lee David Klenerman Simon J. Davis |
author_sort |
James H. Felce |
title |
Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure |
title_short |
Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure |
title_full |
Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure |
title_fullStr |
Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure |
title_full_unstemmed |
Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure |
title_sort |
receptor quaternary organization explains g protein-coupled receptor family structure |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-09-01 |
description |
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. |
topic |
G protein-coupled receptors stoichiometry BRET single-molecule imaging evolution |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717312147 |
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