Cell surface trafficking of many G protein‐coupled receptors is tightly regulated. Among them, the mandatory heterodimer GABAB receptor for the main inhibitory neurotransmitter, γ‐aminobutyric acid (GABA), is a model. In mammals, its cell surface trafficking is highly controlled by an endoplasmic reticulum retention signal in the C‐terminal intracellular region of the GB1 subunit that is masked through a coiled‐coil interaction with the GB2 subunit. Here, we investigate the molecular basis for the export of its homolog in Drosophila melanogaster that regulates the circadian rhythm and sleep. In contrast to mammals, the endoplasmic retention signal is carried by GB2, while GB1 reaches the cell surface alone. NMR analysis showed that the coiled‐coil domain that controls GABAB heterodimer formation is structurally conserved between flies and mammals, despite specific features. These findings show the adaptation of a similar quality control system during evolution for maintaining the subunit composition of a functional heterodimeric receptor.

中文翻译：

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GABA B 受体在进化过程中不同质量控制机制的结构基础

许多 G 蛋白偶联受体的细胞表面运输受到严格调控。其中，主要抑制性神经递质γ-氨基丁酸（GABA）的强制性异二聚体GABAB受体是一个模型。在哺乳动物中，其细胞表面运输受 GB1 亚基 C 端细胞内区域内质网滞留信号的高度控制，该信号通过与 GB2 亚基的卷曲螺旋相互作用被掩盖。在这里，我们研究了在调节昼夜节律和睡眠的黑腹果蝇中输出其同源物的分子基础。与哺乳动物不同，内质滞留信号由 GB2 携带，而 GB1 仅到达细胞表面。核磁共振分析表明，控制 GABAB 异二聚体形成的卷曲螺旋结构域在果蝇和哺乳动物之间在结构上是保守的，尽管有特定的功能。这些发现表明在进化过程中采用了类似的质量控制系统来维持功能性异二聚体受体的亚基组成。