Heterologous expression of many G‐protein coupled receptors (GPCRs) is a major bottleneck in drug discovery efforts for therapeutic development of the receptor. The goal of this study was to utilize domains from a well‐trafficked GPCR to aid in improving the trafficking of a related receptor. The adenosine A_2a receptor (A_2aR) shows exceptional expression and trafficking to the plasma membrane in yeast; however, this is not the case for other adenosine receptors. A_2aR has a longer C‐terminus than the other adenosine receptors, which may contribute to its exceptional trafficking to the plasma membrane. To test the possibility to improve trafficking of the adenosine A₁ receptor (A₁R), chimeric receptors containing the seven transmembrane domains of A₁R and the full‐length or truncated A_2aR C‐terminus were constructed. The chimeric receptor showed improved localization to the plasma membrane and was capable of binding radioligand with native A₁R affinity. Functionally active A₁R receptor variants were produced at a theoretical yield of 95 pmol/mg total membrane protein, estimated using radioligand binding data, which are greater than three‐fold higher than previously reported yields from other heterologous expression systems, and should facilitate biophysical characterization and drug discovery efforts. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4297–4307, 2018

中文翻译：

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A2aR C末端可提高腺苷受体嵌合体的总表达量和活性表达量

许多G蛋白偶联受体（GPCR）的异源表达是该受体治疗性开发的药物开发努力中的主要瓶颈。这项研究的目的是利用人口贩运的GPCR中的结构域来帮助改善相关受体的运输。腺苷A _2a受体（A _2a R）在酵母中表现出非凡的表达和向质膜的运输。但是，其他腺苷受体却不是这种情况。甲_2A R具有一个较长的C-末端比其他腺苷受体，其可以有助于其特殊的运输至质膜。测试改善腺苷A ₁受体（A ₁R），构建了包含A ₁ R的七个跨膜结构域和全长或截短的A _2a R C末端的嵌合受体。嵌合受体显示出改善的质膜定位，并能够以天然的A ₁ R亲和力结合放射性配体。使用放射性配体结合数据估计，具有功能活性的A ₁ R受体变异体的理论产量为95 pmol / mg总膜蛋白，比以前报道的其他异源表达系统的产量高三倍，并且应该促进生物物理表征和药物发现工作。©2018美国化学工程师学会AIChE J，64：4297-4307，2018