Structural study of ganglioside/phospholipid/protein mixture

在本项目中，我们利用同步辐射X射线和中子散射技术研究了贵重生物脂类胶束体系。在这里，我们治疗两种不同类型的贵重生物脂质。一种是神经节苷脂，另一种是磷脂酰肌醇4，5-双(磷酸盐)(PIP_2)。神经节苷脂通过多种神经节苷脂结构参与细胞表面的多种重要生理功能，如组织自组织、免疫反应和细胞分化等。PIP_2是一种酸性磷脂，存在于脑和肾脏细胞膜中，含量较高，近年来作为细胞信号转导中第二信使的来源引起了人们的极大兴趣。这两种基因都在细胞表面的各种生理事件和信号转导中发挥重要作用。我们发现，在生理学条件下，这些脂类在相行为中表现出显著的功能性，这表明…这些脂类更有能力作为膜活性调节剂，通过高度的构象灵活性改变或调节膜-膜相互作用、蛋白质-膜结合、蛋白质-蛋白质相互作用，以响应温度、pH、离子强度和离子种类的局部扰动。例如，我们发现温度的升高导致神经节苷脂胶束的亲水区显著缩小，同时疏水区略有扩大，这表明神经节苷脂分子中含有唾液酸残基的寡糖链对温度的变化做出了敏感的反应。我们还发现，上述收缩伴随着神经节苷脂胶束亲水区域的强烈挤出。在对上述胶束体系的散射数据分析中，我们发展了一种结合重标平均球近似(RMSA)下排斥粒子间相互作用势的壳层模拟方法。我们已经成功地证明了这种方法的高效性，可以直接从实验散射数据中确定胶束内结构和胶束间相互作用。该项目的总结见M.Hirai的综述论文(膜1998，23：8-16)。较少

In this project, we have studied noble biological lipid micellar systems by using both synchrotron X-ray and neutron scattering techniques. Here we treat two different types of noble biological lipids. One is gangliosides and the other is phosphatidylinositol 4,5-bis(phosphaie) (PIP_2). Gangliosidis are Known to participate in various important physiological functions in cell surfaces such as self-organization of tissues, immune response and cell differntiation through a numerous variety of ganglioside structures. PIP_2 is known to be an acidic phospholipid existing at high contents in the cell membranes of brains and kidneys and recently have been attracting strong interests as the source of the second messenger in cellular signal transduction. Both of which are known to play an important role in various physiological events and signal transduction in cell surface. We found that these lipids show remarkable functionality in phase behaviors under physilolgical conditions, suggesting an … More ability of these lipids as a mimbrane active modulator that varies or regulates mimbrane-membrane interaction, protein-membrane binding, protein-protein interaction in membrane through a high conformational flexibility responding to some local perturbation in temperature, pH,ionic strength and ion species. For example, we have found that the elevation of temperature induces a significant shrinkage of the hydrophilic region of the ganglioside micelle accompanied by a slight expansion of the hydrophobic region, indicating that the oligoraccharide chains with sialic acid residues of ganglioside molecules change the conformation sensitively responding to a change of temperature. We have also found that the above shrinkage accompanies an intensive extrusion of water occluded in hydrophilic region of ganglioside micelle. In tne scattering data analyzes of the above micellar systems, we have developed a shell-modeling method combined with a repulsive interparticle interaction potential under a rescaled mean spherical approximation (RMSA) for charged particle dispersions. Wehave demonstrate successfully the high availability of this method for determining both intramicellar structure and intermicellar interaction directly from experimental scattering data. The summery of this project is given in the review paper by M.Hirai(Membrane 1998,23 : 8-16). Less