Structural study of ganglioside/phospholipid/protein mixture

在本项目中，我们利用同步加速器x射线和中子散射技术研究了高贵的生物脂质胶束体系。这里我们讨论两种不同类型的高贵生物脂。一种是神经节苷类，另一种是磷脂酰肌醇4,5-二（磷酸）（PIP_2）。神经节苷脂通过多种多样的神经节苷脂结构参与细胞表面的各种重要生理功能，如组织的自组织、免疫反应和细胞分化。PIP_2是一种酸性磷脂，在大脑和肾脏的细胞膜中含量很高，近年来作为细胞信号转导的第二信使而引起了人们的强烈兴趣。两者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。我们发现这些脂类在生理条件下表现出显著的相行为功能，表明这些脂类更有能力作为膜主动调节剂，通过对温度、pH、离子强度和离子种类等局部扰动的高构象灵活性，改变或调节膜-膜相互作用、蛋白-膜结合、膜内蛋白-蛋白相互作用。例如，我们发现温度升高会导致神经节苷脂胶束的亲水性区域显著收缩，同时疏水性区域略有扩张，这表明具有神经节苷脂分子唾液酸残基的寡糖链会敏感地响应温度变化而改变构象。我们还发现，上述收缩伴随着封闭在神经节苷脂胶束亲水性区域的水的密集挤压。在上述胶束体系的散射数据分析中，我们开发了一种结合重标平均球近似（RMSA）下的粒子间斥力相互作用势的壳模型方法。我们已经成功地证明了这种方法的高可用性，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。M.Hirai（Membrane 1998,23: 8-16）的综述文章对该项目进行了总结。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