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Structural study of ganglioside/phospholipid/protein mixture

神经节苷脂/磷脂/蛋白质混合物的结构研究

基本信息

批准号：
08680712
负责人：
HIRAI Mitsuhiro
金额：
$ 1.54万
依托单位：
GUNMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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

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金属生物脂质胶束体系。在这里，我们处理两种不同类型的高贵的生物脂质。一种是神经节苷脂，另一种是磷脂酰肌醇4，5-二（磷脂）（PIP_2）。已知神经节苷脂通过多种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、免疫应答和细胞分化。PIP_2是一种酸性磷脂，在脑和肾的细胞膜中含量很高，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。它们在细胞表面的各种生理活动和信号转导中起着重要作用。我们发现，这些脂质在生理条件下的相行为中显示出显著的功能性，这表明 ...更多信息这些脂质作为膜活性调节剂的能力，其通过响应温度、pH、离子强度和离子种类中的一些局部扰动的高构象柔性来改变或调节膜-膜相互作用、蛋白质-膜结合、膜中的蛋白质-蛋白质相互作用。例如，我们已经发现，温度的升高引起神经节苷脂胶束的亲水区域的显著收缩，伴随着疏水区域的轻微膨胀，这表明神经节苷脂分子的具有唾液酸残基的寡糖链敏感地响应于温度的变化而改变构象。我们还发现，上述收缩伴随着神经节苷脂胶束亲水区的水的强烈挤出。在上述胶束体系的散射数据分析中，我们发展了一种在重标平均球近似（RMSA）下结合排斥性粒子间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，直接从实验散射数据确定胶束内结构和胶束间的相互作用。在M.Hirai的综述论文（Membrane 1998，23：8-16）中给出了该项目的总结。少