CALCIUM DEPENDENT MEMBRANE BINDING PROTEINS

描述(摘自摘要)：钙依赖，磷脂结合 与生物膜相关的蛋白质响应细胞激活和 钙离子进入细胞质。该项目的目标是确定 这两类化合物的结构和生物活性 蛋白质、膜联蛋白和含有C2结构域的蛋白质。X射线 结晶学将被用来确定膜联蛋白II的结构 突触素的细胞质结构域，以及Copins。电子显微镜观察 这些蛋白质在脂单分子层上的二维晶体将被用于 确定这些蛋白质与之相互作用的物理性质 膜。单个蛋白质结构域在促进脂肪生成中的作用 相互作用和特异性将由蛋白质的突变来决定。 以及对模型膜系统的研究。与之相互作用的蛋白质 受膜联蛋白和Copine的调控将具有特征性。本土化 以及这些膜结合蛋白在活细胞和组织中的运动 将会被确定。将研究膜联蛋白和粘连蛋白的功能。 通过基因沉默的方法在两种模式生物，线虫线虫， 和纤毛虫草履虫。这些外围蛋白是 被假设为调节或调节在膜表面发生的事件 刺激的细胞。因此，这些研究应该提供对基础知识的洞察 膜转运和信号调控的机制 在正常细胞和病理细胞中发生的跨膜转导 疾病包括癌症、神经性高血压、糖尿病和其他 内分泌失调。

DESCRIPTION (Adapted from abstract): Calcium-dependent, phospholipid-binding proteins associate with biological membranes in response to cell activation and calcium entry into the cytoplasm. The goal of this project is to determine the structures and biological activities of two ubiquitous classes of these proteins, the annexins, and C2-domain containing proteins. X-ray crystallography will be used to determine the structures of annexin II, the cytoplasmic domain of synaptotagmin, and the copines. Electron microscopy of 2-dimensional crystals of these proteins on lipid monolayers will be used to determine the physical nature of the interaction of these proteins with membranes. The role of individual protein domains in promoting lipid interaction and specificity will be determined by mutagenesis of the proteins and studies on model membrane systems. Proteins that interact with and are regulated by the annexins and copines will be characterized. The localization and movements of these membrane-binding proteins in living cells and tissues will be determined. The functions of the annexins and copines will be studied by genetic silencing methods in two model organisms, the nematode C. elegans, and the ciliate Paramecium tetaurelia. These peripheral proteins are hypothesized to mediate or regulate events occurring on membrane surfaces in stimulated cells. Therefore, these studies should provide insights into basic mechanisms underlying the regulation of membrane trafficking and signal transduction across membranes occurring in normal cells and in pathological conditions including cancer, neurogenic hypertension, diabetes and other endocrine disorders.