Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure

Cell Reports

David Klenerman¹  Steven F. Lee¹  Sarah L. Latty¹  Susan R. Mattick²  James H. Felce²  Rachel G. Knox²  Simon J. Davis²  Yuan Lui² 

[1] Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK;Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK;

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

DOI  :  10.1016/j.celrep.2017.08.072

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown