The heteromeric GABA-B receptor recognizes G-protein α subunit C-termini
The heteromeric GABA-B receptor recognizes G-protein α subunit C-termini
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DOI：
10.1016/s0028-3908(99)00135-5
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发表时间：
1999-11-01
影响因子：
4.7
通讯作者：
Blahos, J
中科院分区：
文献类型：
--
作者：
Franek, M;Pagano, A;Blahos, J
最近克隆的GABA-B受体与代谢性谷氨酸受体(mGlu受体)、钙敏感受体和一组犁鼻受体相关。GABA-B受体可能以异二聚体的形式起作用，由GABA-BR1和GABA-BR2组成。G蛋白偶联受体(GPCRs)结构的这一新特征引发了关于这种受体识别G蛋白的机制的问题。在本研究中，我们证明了GABA-BR1和BR2亚基形成了一个功能性受体，当在HEK293细胞中表达时，该受体识别GαI和GαO蛋白的极端C末端。事实上，异构体GABA-BR1/BR2受体在与GαQ共表达时不激活PLC，但当与嵌合的Gαq5或Gαqo5亚基共表达时激活PLC，GαQ亚基中的5个C-末端残基分别是Gα1或Gα0的亚基。有趣的是，异构体GABA-B受体不激活包含Gαz的5个C末端残基的嵌合Gαqz5亚基。在Gαqo5和Gαqz5之间的三个不同的残基(-5、-4和-1)中，Gαo蛋白-4位的氨基酸残基是决定与受体偶联选择性的关键，残基-5影响偶联效率。有趣的是，这些发现与mGluR2受体的数据相符，mGluR2受体是GABA-B蛋白的远亲。这表明，G蛋白α亚基的相同分子决定因素参与了异构体GABA-B受体和其他GPCRs的特异性识别。(C)1999爱思唯尔科学有限公司。保留所有权利。
The recently cloned GABA-B receptors are related to the metabotropic glutamate receptors (mGlu receptors), the Ca2+-sensing receptor and one group of vomeronasal receptors. The GABA-B receptors likely function in a heterodimeric form, constituted of GABA-BR1 and GABA-BR2. This novel feature in the G-protein coupled receptors (GPCRs) structure raises questions as to the mechanism of recognition of G-proteins by such receptors. In the present study we show that the GABA-BR1 and BR2 subunits form a functional receptor that recognizes the extreme C-termini of the G alpha i and G alpha o proteins when expressed in HEK293 cells. Indeed, heteromeric GABA-BR1/BR2 receptors do not activate PLC when co-expressed with G alpha q, but do so when co-expressed with the chimeric G alpha qi5 or G alpha qo5 subunits, the G alpha q subunit in which the 5 C-terminal residues are those of G alpha i or G alpha o, respectively. Interestingly, the heteromeric GABA-B receptor did not activate the chimeric G alpha qz5 subunit that contains the 5 C-terminal residues of G alpha z. Among the three residues that are distinct between G alpha qo5 and G alpha qz5 (at position - 5, - 4 and - 1), the amino acid residue at position - 4 of G alpha o proteins is critical for specifying the coupling selectivity with the receptor and residue -5 influences the coupling efficacy. Interestingly, these findings correspond to data obtained with the mGluR2 receptor, a distant relative of GABA-B proteins. This shows that the same molecular determinants of the G-protein alpha-subunits are involved in the specific recognition of both the heteromeric GABA-B receptors and the other GPCRs. (C) 1999 Elsevier Science Ltd. All rights reserved.