Sarramegn V, Muller I, Milon A, Talmont F
UMR 5089, Institut de Pharmacologie et de Biologie Structurale, 205, route de Narbonne, 31077, Toulouse, cedex 4, France.
Cell Mol Life Sci. 2006 May;63(10):1149-64. doi: 10.1007/s00018-005-5557-6.
G protein-coupled receptors (GPCRS) represent a class of integral membrane proteins involved in many biological processes and pathologies. Fifty percent of all modern drugs and almost 25% of the top 200 bestselling drugs are estimated to target GPCRs. Despite these crucial biological implications, very little is known, at atomic resolution, about the detailed molecular mechanisms by which these membrane proteins are able to recognize their extra-cellular stimuli and transmit the associated messages. Obviously, our understanding of GPCR functioning would be greatly facilitated by the availability of high-resolution three-dimensional (3D) structural data. However, expression, solubilization and purification of these membrane proteins are not easy to achieve, and at present, only one 3D structure has been determined, that of bovine rhodopsin. This review presents and compares the different successful strategies which have been applied to solubilize and purify recombinant GPCRs in the perspective of structural biology experiments.
G蛋白偶联受体（GPCRs）是一类参与许多生物过程和病理过程的整合膜蛋白。据估计，所有现代药物中有50%以及最畅销的200种药物中近25%都以GPCRs为靶点。尽管这些受体具有如此关键的生物学意义，但在原子分辨率下，对于这些膜蛋白识别细胞外刺激并传递相关信息的详细分子机制却知之甚少。显然，高分辨率三维（3D）结构数据的可得性将极大地促进我们对GPCR功能的理解。然而，这些膜蛋白的表达、溶解和纯化并非易事，目前仅确定了一种3D结构，即牛视紫红质的结构。本文从结构生物学实验的角度介绍并比较了用于溶解和纯化重组GPCRs的不同成功策略。
