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: 6621068
• 负责人: CURTIS Fred BREWER
• 金额: $ 45.94万
• 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/6621068
• 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.

描述：(申请人提供)：低聚糖链 正常细胞和转化细胞的糖蛋白和糖脂已被显示 是各种生物过程中的受体，包括细胞 识别、黏附、凋亡、分化和致癌转化。 其中许多生物效应是由于糖共轭化合物的相互作用造成的。 受体和凝集素是碳水化合物结合蛋白。多价的 凝集素的结合特性通常会导致凝集素的交联和聚集 细胞表面糖结合受体及其伴随的信号转导 效果。分子和结构研究表明，某些凝集素形成 具有特定多价低聚糖的均相交联络合物 和糖蛋白，即使在分子混合物的存在下也是如此。近期 X射线结晶学研究证明了独一无二的 凝集素与A之间的二维和三维交联晶格 一系列多价碳水化合物。教育部最近观察到 人T细胞表面的几种特异性糖蛋白受体 通过结合和交联剂进行分离和选择性聚集 Galectin-1，一种内源性二聚体凝集素，导致细胞死亡。这个 Galectin-1诱导不同计数器的分离和选择性聚集 与磷酸酶或激酶活性相关的受体是 使用我们的凝集素-碳水化合物交联的分子研究进行建模 互动。这些和其他观察表明，选择性的 Galectin-1与Galectin家族其他成员的交联性 在它们的生物学活动中很重要。这项提议的目标是 确定精细的碳水化合物结合特性、交联性和 半乳糖凝集素及其相关凝集素的物理性质 它们在正常细胞和转化细胞中的构效关系。