US-UK Cooperative Research: Identification of Ligands for Carbohydrate-Recognition Domains

该奖项将支持哥伦比亚大学的Kurt Drickamer博士和英格兰米德尔塞克斯哈罗医学研究委员会临床研究中心的Ten Feizi博士在生物化学方面的合作研究。该项目的目标是研究被称为哺乳动物凝集素的某些动物蛋白的详细碳水化合物结合特性。在具有多种生物学功能的蛋白质中发现了一种常见的碳水化合物识别结构域(CRD)。含有这些同源结构域的蛋白质包括血清甘露糖结合蛋白和肝膜受体，后者介导去唾液酸糖蛋白的内吞作用。根据一级结构信息，CRD在其他蛋白质中也被预测和发现，如肺表面活性物质载脂蛋白和软骨蛋白多糖的核心蛋白。美国首席研究员_的实验室正在开发在大肠杆菌中产生这些结构域的表达系统。在这个项目中，建议与Ten Feizi博士合作；他的研究小组开发了一种印迹新糖脂的方法，该方法将使研究人员能够确定各种CRD的详细糖结合特异性，并将用于识别结构域的内源配体。通过将Drickamer博士实验室的蛋白质和分子生物学专业知识与Feizi博士团队的碳水化合物技术相结合，将有可能启动一种强大的新方法来分析碳水化合物识别的生物学作用。Drickamer博士是哺乳动物凝集素和相关蛋白质分子生物学领域的领导者，他已经证明了他有能力使用重组DNA方法来表达这些蛋白质的碳水化合物结合域。

This award will support collaborative research in biochemistry between Dr. Kurt Drickamer, Columbia University and Dr. Ten Feizi, Medical Research Council Clinical Research Center, Harrow, Middlesex, England. The objective of the project is to study the detailed carbohydrate binding specificities of certain animal proteins called mammalian lectins. A type of common carbohydrate-recognition domain (CRD) has been identified in proteins with diverse biological functions. Proteins containing these homologous domains include serum mannose binding proteins and the hepatic membrane receptor, which mediates endocytosis of asialoglycoproteins. Based on primary structure information, CRDs have been predicted and found in other proteins, such as pulmonary surfactant apoprotein and core protein of cartilage proteoglycan. Expression systems for producing these domains in Eschericia coli are being developed in the laboratory of _______________ the principal investigator in the United States. In this project, a collaboration is proposed with Dr. Ten Feizi; his research group has developed a method of blotting neoglycolipids which will allow the investigators to determine the detailed saccharide-binding specificity of the various CRDs and which will also be used to identify endogenous ligands for the domains. By combining the protein and molecular biology expertise of Dr. Drickamer's laboratory with the carbohydrate technology of Dr. Feizi's group, it will be possible to initiate a powerful new approach to analysis of the biological role of carbohydrate recognition. Dr. Drickamer is a leader in the molecular biology of mammalian lectins and related proteins and has demonstrated his ability to use recombinant DNA approaches for expression of the carbohydrate binding domain of these proteins.