Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Cell Rep. 2017 Sep 12;20(11):2654-2665. doi: 10.1016/j.celrep.2017.08.072.
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.
细胞表面视紫红质家族 G 蛋白偶联受体 (GPCR) 的组织形式存在争议。在对大多数单个受体的研究中，都支持或反对二聚体的存在。在这里，我们使用大规模比较研究来检查由单个人类细胞系表达的 60 种受体的化学计量特征。我们使用生物发光共振能量转移和单分子显微镜检测方法，发现相对较少的视紫红质家族 GPCR 作为二聚体存在，而这些受体在其他方面似乎是单体。总体而言，分析预测少于 20%的约 700 个视紫红质家族受体形成二聚体。我们样本中二聚体的聚集分布，以及我们还揭示的受体组织与 GPCR 家族大小之间的惊人相关性，都表明受体的化学计量可能深刻影响了 GPCR 的扩张和多样化。
