Molecular cloning and characterisation of a novel GABAB-related G-protein coupled receptor
Molecular cloning and characterisation of a novel GABAB-related G-protein coupled receptor
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DOI：
10.1016/s0169-328x(02)00662-9
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发表时间：
2003-02-20
期刊：
影响因子：
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通讯作者：
Pangalos, MN
中科院分区：
文献类型：
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作者：
Calver, AR;Michalovich, D;Pangalos, MN
利用基于同源性的生物信息学方法，我们分析了人类基因组序列，并鉴定了一种新的假定的七个跨膜G蛋白偶联受体的人和啮齿动物的同源物，称为GABA(BL)。根据这些cDNA与GABA(B1)和GABA(B2)的氨基酸序列同源性，我们推测GABA(BL)是一个新的GABA(B)受体亚基。GABA(BL)的C端序列含有一个可能的卷曲结构域、二亮氨酸和几个RXR(R)ER保留基序，所有这些都被证明在GABA(A)受体亚单位的功能中起关键作用。此外，GABA(BL)在中枢神经系统的分布与其他已知的GABA(B)亚单位的分布相似。然而，当GABA(BL)单独表达时，或者在GABA(B1)或GABA(B2)存在的情况下，我们无法检测到任何GABA(B)配体反应的受体功能。因此，如果GABA(BL)确实是一个GABA(B)受体亚单位，那么它的伴侣就是一个潜在的新的受体亚单位或伴侣蛋白，但尚未被鉴定。(C)2002 Elsevier Science B.V.保留所有权利。
Using a homology-based bioinformatics approach we have analysed human genomic sequence and identified the human and rodent orthologues of a novel putative seven transmembrane G protein coupled receptor, termed GABA(BL). The amino acid sequence homology of these cDNAs compared to GABA(B1), and GABA(B2) led us to postulate that GABA(BL) was a putative novel GABA(B) receptor subunit. The C-terminal sequence of GABA(BL) contained a putative coiled-coil domain, di-leucine and several RXR(R) ER retention motifs, all of which have been shown to be critical in GABA(A) receptor subunit function. In addition, the distribution of GABA(BL) in the central nervous system was reminiscent of that of the other known GABA(B) subunits. However, we were unable to detect receptor function in response to any GABA(B) ligands when GABA(BL) was expressed in isolation or in the presence of either GABA(B1) or GABA(B2). Therefore, if GABA(BL), is indeed a GABA(B) receptor subunit, its partner is a potentially novel receptor subunit or chaperone protein which has yet to be identified. (C) 2002 Elsevier Science B.V. All rights reserved.