CARBOHYDRATE AND GLYCOPROTEIN INTERACTIONS WITH LECTINS

碳水化合物和糖蛋白与凝集素的相互作用

• 批准号: 6686432
• 负责人: CURTIS Fred BREWER
• 金额: $ 46.81万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-07-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6686432
• 关键词: X ray crystallography; analytical ultracentrifugation; apoptosis; carbohydrate receptor; carbohydrates; cell growth regulation; cell proliferation; chemical structure function; chemical synthesis; crosslink; electron microscopy; glycoproteins; intermolecular interaction; lectin; microcalorimetry; neuroblastoma; protein purification; receptor expression; recombinant proteins; stoichiometry; structural biology; thermodynamics; tissue /cell culture

DESCRIPTION: (provided by applicant): the oligosaccharide chains of glycoproteins and glycolipids of normal and transformed cells have been shown to be receptors in a variety of biological processes, including cellular recognition, adhesion, apoptosis, differentiation and oncogenic transformation. Many of these biological effects are due to the interaction of glycoconjugate receptors with lectins which are carbohydrate binding proteins. The multivalent binding properties of lectins often results in cross-linking and aggregation of cell surface glycoconjugate receptors and concomitant signal transduction effects. Molecular and structural studies have shown that certain lectins form homogeneous cross-linked complexes with specific multivalent oligosaccharides and glycoproteins, even in the presence of mixtures of the molecules. Recent x-ray crystallographic studies have demonstrated the formation of unique crystalline 2- and 3-dimensional cross-linked lattices between lectins and a series of multivalent carbohydrates. Moe recently it has been observed that several specific glycoprotein receptors on the surface of human T cells undergo separation and selective clustering by the binding and cross-linking of galectin-1, an endogenous dimeric lectin, resulting in cell death. The galectin-1 induced separation andselective clustering of different counter receptors which are associated with phosphatase or kinase activities was modeled using our molecular studies of lectin-carbohydrate cross-linking interactions. These and other observations suggest that the selective cross-linking properties of galectin-1 and other members of the galectin family are important in their biological activities. The goal of this proposal is to determine the fine carbohydrate binding specificities, cross-linking and physical properties of galectins and related lectins in order to understand their structure-activity properties in normal and transformed cells.

性状：（由申请人提供）： 正常和转化细胞的糖蛋白和糖脂 在多种生物过程中，包括细胞内， 识别、粘附、凋亡、分化和致癌转化。 这些生物学效应中的许多是由于糖缀合物的相互作用 受体与凝集素，这是碳水化合物结合蛋白。多价 凝集素的结合特性通常会导致交联和聚集 细胞表面糖缀合物受体和伴随的信号转导 方面的影响.分子和结构研究表明，某些凝集素 具有特定多价寡糖的均相交联复合物 和糖蛋白，甚至在分子混合物的存在下。最近 X射线晶体学研究表明， 晶体2-和3-维交联晶格之间的凝集素和一个 一系列多价碳水化合物。莫伊最近观察到， 人T细胞表面上的几种特异性糖蛋白受体 通过结合和交联的分离和选择性聚集 半乳糖凝集素-1，一种内源性二聚凝集素，导致细胞死亡。的 galectin-1诱导的不同计数器的分离和选择性聚类 与磷酸酶或激酶活性相关的受体， 使用我们的凝集素-碳水化合物交联的分子研究建模 交互.这些和其他观察表明，选择性 半乳糖凝集素-1和半乳糖凝集素家族其它成员的交联性质 在其生物学活动中非常重要。本提案的目的是 确定精细的碳水化合物结合特异性、交联和 半乳糖凝集素和相关凝集素的物理性质，以便了解 它们在正常和转化细胞中的结构-活性特性。