Lagane B, Gaibelet G, Meilhoc E, Masson J M, Cézanne L, Lopez A
Institut de Pharmacologie et de Biologie Structurale, CNRS INSA UMR 5089, 205 Route de Narbonne, 31077 Toulouse cedex, France.
J Biol Chem. 2000 Oct 27;275(43):33197-200. doi: 10.1074/jbc.C000576200.
This study provides evidence that the differences in membrane composition found from one cell type to another can represent a limiting factor to recovering the functionality of transmembrane proteins when expressed in heterologous systems. Restoring the properties of the human mu-opioid receptor in yeast (Saccharomyces cerevisiae), similar to those observed in native cells, was achieved by replacing ergosterol from yeast by cholesterol, which is normally found in mammalian plasma membranes. The results suggest that these two sterols have opposite effects with respect to the ligand binding function of the receptor. Ergosterol was found to constrain the mu-opioid receptor in an inactive state in yeast plasma membranes and cannot replace cholesterol in activating it. These data differ from previous works dealing with the function of related G-protein-coupled receptors (GPCR) in ergosterol-enriched membranes. This suggests that structural requirements of GPCR with respect to their modulation by lipid components differ from one protein to another. As a consequence, we assume that the presence of appropriate lipids around transmembrane proteins determines their function. This highlights the functional significance of lateral heterogeneities of membrane components within biological membranes.
本研究提供了证据，表明从一种细胞类型到另一种细胞类型发现的膜组成差异可能是在异源系统中表达时恢复跨膜蛋白功能的限制因素。通过用通常存在于哺乳动物质膜中的胆固醇替代酵母中的麦角固醇，在酵母（酿酒酵母）中恢复了与天然细胞中观察到的类似的人μ-阿片受体特性。结果表明，这两种固醇对受体的配体结合功能具有相反的作用。发现麦角固醇在酵母质膜中将μ-阿片受体限制在无活性状态，并且在激活受体时不能替代胆固醇。这些数据与之前关于富含麦角固醇的膜中相关G蛋白偶联受体（GPCR）功能的研究不同。这表明GPCR对脂质成分调节的结构要求因蛋白质而异。因此，我们假设跨膜蛋白周围存在合适的脂质决定了它们的功能。这突出了生物膜内膜成分横向异质性的功能意义。
