A G Protein-Coupled Receptor Dimerization Interface in Human Cone Opsins
A G Protein-Coupled Receptor Dimerization Interface in Human Cone Opsins
复制标题
DOI：
10.1021/acs.biochem.6b00877
复制
发表时间：
2017-01-10
期刊：
影响因子：
2.9
通讯作者：
Smith, Adam W.
中科院分区：
文献类型：
--
作者：
Jastrzebska, Beata;Comar, William D.;Smith, Adam W.
G蛋白偶联受体(GPCRs)检测各种物理和化学信号，并通过细胞膜传递这些信息。二聚化是一种被认为是GPCR信号的调节器，但A类GPCR二聚体的结构和稳定性一直难以确定。在这里，我们研究了启动和维持白天色觉的人视锥蛋白的二聚化亲和力和结合界面。使用时间分辨荧光方法，我们发现人的红色视锥视蛋白表现出很强的二聚化倾向，而绿色视锥视蛋白和蓝色视锥视蛋白则没有。通过诱变实验，我们在人红色视锥蛋白的第五个跨膜螺旋上发现了一个二聚化界面，涉及氨基酸1230、A233和M236。对红色视锥视蛋白这一界面的洞察应该有助于正在进行的细胞信号中GPCR四元相互作用的结构和功能的研究。最后，我们证明了二聚化所需的相同残基也是红锥视蛋白光谱调谐的部分原因。这最后一个观察结果有可能为研究红色锥体视蛋白的二聚化的功能作用开辟新的途径。
G protein-coupled receptors (GPCRs) detect a wide variety of physical and chemical signals and transmit that information across the cellular plasma membrane. Dimerization is a proposed modulator of GPCR signaling, but the structure and stability of class A GPCR dimerization have been difficult to establish. Here we investigated the dimerization affinity and binding interface of human cone opsins, which initiate and sustain daytime color vision. Using a time-resolved fluorescence approach, we found that human red cone opsin exhibits a strong propensity for dimerization, whereas the green and blue cone opsins do not. Through mutagenesis experiments, we identified a dimerization interface in the fifth transmembrane helix of human red cone opsin involving amino acids 1230, A233, and M236. Insights into this interface of red cone opsin should aid ongoing investigations of the structure and function of GPCR quaternary interactions in cell signaling. Finally, we demonstrated that the same residues needed for dimerization are also partially responsible for the spectral tuning of red cone opsin. This last observation has the potential to open up new lines of inquiry regarding the functional role of dimerization for red cone opsin.