CARBOHYDRATE AND GLYCOPEPTIDE INTERACTIONS WITH LECTINS

碳水化合物和糖肽与凝集素的相互作用

• 批准号: 3164341
• 负责人: CURTIS Fred BREWER
• 金额: $ 30.5万
• 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 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3164341
• 关键词: X ray crystallography; binding proteins; carbohydrate receptor; carbohydrate structure; carbohydrates; chemical binding; chemical models; circular dichroism; concanavalin A; conformation; crosslink; electron microscopy; electron spin resonance spectroscopy; galactose; glycolipids; glycopeptides; glycoprotein structure; lectin; mannose; membrane activity; nuclear magnetic resonance spectroscopy; oligosaccharides; protein structure function; radiotracer

The oligosaccharide chains of glycoproteins and glycolipids of normal and transformed cells have been implicated as receptors in a variety of biological processes including cellular recognition and adhesion, differentiation, and oncogenic transformation. Although the structures of many of the carbohydrates have been determined, little is known about their molecular binding properties, other than their interactions with glycosylases, which regulate their biosynthesis, and lectins, which are carbohydrate binding proteins. Lectins are found in plants, bacteria, and normal and transformed animal cells. Lectin binding to the surface of cells often leads to cross-linking of glycoconjugate receptors, including glycoproteins and glycolipids, which, in many cases, is related to the biological responses of the cells. Recently, we have shown that certain oligosaccharides isolated from glycoproteins and glycolipids are multivalent and can cross-link and precipitate with lectins. We have demonstrated that this leads to an important new dimension of specificity in carbohydrate-protein interactions: namely, the formation of a unique, homogeneous cross-linked complex between each carbohydrate and lectin, even in the presence of mixtures of the molecules. Furthermore, the precipitates are often crystalline and can be investigated by electron microscopy and x-ray diffraction techniques. Our preliminary studies demonstrate that information on the structures of carbohydrate-lectin cross-linked complexes can be obtained, including the symmetries, and geometries of the lattice, the conformation of bound carbohydrates, and possible protein-protein interactions that stabilize the lattice. The latter findings suggest that the structures of certain lectins near their carbohydrate binding sites are designed to facilitate these cross-linking interactions. Our results also indicate that lectins form similar lattices with glycoproteins by carbohydrate mediated cross-linking. Thus, the goal of this proposal is a biophysical investigation of the molecular mechanisms of binding and cross- linking of lectins with multivalent oligosaccharides and glycoconjugates. The results, in turn, will provide insight into their interactions in biological systems.

正常和正常的糖蛋白和糖脂的寡糖链 转化的细胞作为受体参与了多种 包括细胞识别和黏附在内的生物过程， 分化和致癌转化。尽管它的结构 许多碳水化合物已经被测定，但人们对它们的了解很少 分子结合特性，而不是它们与 糖基酶，调节其生物合成，以及凝集素，这是 碳水化合物结合蛋白。凝集素存在于植物、细菌和 正常和转化的动物细胞。凝集素与细胞表面的结合 细胞常常导致糖共轭受体的交联化，包括 糖蛋白和糖脂，在许多情况下，与 细胞的生物学反应。 最近，我们已经证明了从植物中分离出来的某些寡糖 糖蛋白和糖脂是多价的，可以交联和 用凝集素沉淀。我们已经证明，这将导致 碳水化合物-蛋白质专一性的重要新维度 相互作用：即形成独特的、同质的交联体 每种碳水化合物和凝集素之间的复合体，即使在 分子的混合物。此外，沉淀物通常是 晶体，可以用电子显微镜和x射线进行研究。 衍射技术。我们的初步研究表明 碳水化合物-凝集素交联物的结构信息 可以得到，包括晶格的对称性和几何形状， 结合碳水化合物的构象，以及可能的蛋白质-蛋白质 稳定晶格的相互作用。后一项研究结果表明 某些凝集素在其碳水化合物结合部位附近的结构如下 旨在促进这些交叉链接的相互作用。我们的结果也是 表明凝集素通过与糖蛋白形成相似的晶格 碳水化合物介导的交联剂。因此，这项提案的目标是 结合和交叉的分子机制的生物物理研究 凝集素与多价低聚糖和糖偶联物的连接。 反过来，这些结果将使我们深入了解他们在 生物系统。