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CALCIUM DEPENDENT MEMBRANE BINDING PROTEINS

钙依赖性膜结合蛋白

基本信息

批准号：
6519680
负责人：
CARL E CREUTZ
金额：
$ 28.11万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-07-01 至 2005-06-30
项目状态：
已结题

项目摘要

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.

描述（改编自摘要）：钙依赖性、磷脂结合蛋白质与生物膜结合以响应细胞激活和钙进入细胞质。该项目的目标是确定其中两个普遍存在的类别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射线晶体学将用于确定膜联蛋白 II 的结构，突触结合蛋白的细胞质结构域和copine。电子显微镜观察这些蛋白质在脂质单层上的二维晶体将用于确定这些蛋白质相互作用的物理性质膜。单个蛋白质结构域在促进脂质中的作用相互作用和特异性将由蛋白质的诱变决定以及模型膜系统的研究。相互作用的蛋白质受膜联蛋白和copines调节的特征将被表征。本土化以及这些膜结合蛋白在活细胞和组织中的运动将被确定。将研究膜联蛋白和copine的功能通过两种模式生物（线虫秀丽隐杆线虫）的基因沉默方法，和纤毛虫草履虫。这些外周蛋白是假设介导或调节膜表面发生的事件受到刺激的细胞。因此，这些研究应该提供对基础知识的见解。膜运输和信号调节的潜在机制正常细胞和病理细胞中发生的跨膜转导疾病包括癌症、神经源性高血压、糖尿病和其他内分泌失调。