CAROHYDRATE AND GLYCOPROTEIN INTERACTIONS WITH LECTINS

正常人和正常人的糖蛋白和糖脂的寡糖链 转化的细胞已经被认为是多种 生物过程包括细胞识别和粘附， 分化和致癌转化。 虽然结构 许多碳水化合物已被确定，很少有人知道他们的 分子结合特性，而不是它们与 调节其生物合成的糖基化酶，以及 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。 凝集素结合到 细胞内的糖缀合物通常导致糖缀合物受体的交联，包括 糖蛋白和糖脂，这在许多情况下，是有关的， 细胞的生物反应。 最近，我们已经表明，某些寡糖分离，从 糖蛋白和糖脂是多价的，可以交联， 用凝集素沉淀。 我们已经证明，这导致了一个 碳水化合物-蛋白质特异性重要新维度 相互作用：即，形成独特的，均匀的交联 每种碳水化合物和凝集素之间的复合物，即使在存在 分子的混合物。 此外，沉淀物通常是 晶体，并可通过电子显微镜和X射线研究 衍射技术 我们的初步研究表明， 碳水化合物-凝集素交联复合物的结构信息 可以得到，包括对称性，晶格的几何形状， 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位点附近的结构是 旨在促进这些交联相互作用。 我们的研究结果还 表明凝集素与糖蛋白形成类似晶格， 碳水化合物介导的交联。 因此，本提案的目标是 结合和交叉的分子机制的生物物理研究， 凝集素与多价寡糖和糖缀合物的连接。 结果，反过来，将提供洞察他们的相互作用， 生物系统。

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.