Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure.
Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure.
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DOI：
10.1016/j.celrep.2017.08.072
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发表时间：
2017-09-12
期刊：
影响因子：
8.8
通讯作者：
Davis SJ
中科院分区：
文献类型：
--
作者：
Felce JH;Latty SL;Knox RG;Mattick SR;Lui Y;Lee SF;Klenerman D;Davis SJ
视紫红质家族G蛋白偶联受体(GPCRs)在细胞表面的组织结构存在争议。在大多数单个受体的研究中，支持和反对二聚体的存在都得到了支持。在这里，我们使用大规模的比较研究来检验由单个人类细胞系表达的60个受体的化学计量特征。使用生物发光共振能量转移和基于单分子显微镜的分析，我们发现视紫红质家族GPCRs中相对较小的一部分表现为二聚体，而这些受体在其他方面似乎是单体的。总体而言，分析预测，在∼700型视紫红质家族受体中，形成二聚体的不到20%。我们还发现，样本中二聚体的聚集分布以及受体组织和GPCR家族规模之间的显着相关性表明，受体化学计量学可能深刻地影响了GPCR的扩增和多样化。对60个视紫红质家族GPCR的系统分析表明，大多数是单体，视紫红质家族的祖先GPCR也是跨家族的单体，受体多样化的速度与化学计量学相关倾斜的家族结构表明二聚化增加了受体的“适配密度”视紫红质家族GPCR的第四级组织存在争议。Felce等人。显示60种受体大多是单体。他们对GPCR家族结构的显著不对称性提出了一个简单的解释，即它是由单体的谱系扩张支撑的，而不是二聚体的谱系扩张。
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. Systematic analysis of 60 Rhodopsin-family GPCRs reveals that most are monomers Rhodopsin-family root ancestor GPCRs are also monomers Across families, rates of receptor diversification correlate with stoichiometry Skewed family structure suggests dimerization increases receptor “fitness density” 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.
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影响因子：
3.4
作者：
Felce, James H.;Knox, Rachel G.;Davis, Simon J.
通讯作者：
Davis, Simon J.
DOI：
10.1073/pnas.0804286105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Contento, Rita Lucia;Molon, Barbara;Viola, Antonella
通讯作者：
Viola, Antonella
影响因子：
3.6
作者：
Fredriksson, R;Schiöth, HB
通讯作者：
Schiöth, HB
影响因子：
4.4
作者：
Baycin-Hizal, Deniz;Tabb, David L.;Betenbaugh, Michael
通讯作者：
Betenbaugh, Michael
影响因子：
64.5
作者：
Chandrashekar, J;Mueller, KL;Ryba, NJP
通讯作者：
Ryba, NJP