GLYCOPROTEIN IN HORMONE OLIGOSACCHARIDES

激素低聚糖中的糖蛋白

• 批准号: 2905400
• 负责人: JACQUES U BAENZIGER
• 金额: $ 40.6万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2905400
• 关键词: N acetylgalactosamine; affinity labeling; carbohydrate sequence; chemical structure function; chimeric proteins; enzyme mechanism; enzyme structure; glycoprotein structure; glycosylation; glycosyltransferase; hormone regulation /control mechanism; immunoprecipitation; laboratory mouse; laboratory rabbit; laboratory rat; luteinizing hormone; molecular cloning; monoclonal antibody; oligosaccharides; peptide hormone; protein localization; sialyltransferases; sulfotransferase

DESCRIPTION: N-linked oligosaccharides terminating with the sequence S04- 4-GalNAc-beta1, 4GlcNAc-beta (SGN) have been conserved on the glycoprotein hormones of vertebrate species from fish to mammals. This implies that they serve highly important functions whose definition is a long term goal of the applicant's research. These oligosaccharide structures are recognized by an SGN-specific receptor, and play an essential role in vivo, for example, in regulating LH circulating half life to maximize its receptor activation during the ovulatory cycle. The highly regulated synthesis of these structures yields a family of oligosaccharides containing the sequence GalNAc-beta1, 4-GlcNAc-beta initiated by protein specific beta1, 4GalNAc transferase on selected glycoproteins. Three distinct family members can be produced by the subsequent addition of S04, sialic acid, or fucose by protein-independent transferases such as the GalNAc-4-sulfo transferase. This project will pursue two major specific aims: 1). A definition of the molecular basis for regulation of protein- specific and protein-independent forms of glycosylation by the beta1, 4GalNAc-T and the GalNAc-sulfoT in vitro and in vivo, and 2). Molecular definition of the structural features of the protein specific beta1, 4GalNAc transferase and the protein independent GalNAc-4-sulfoT that account for their properties and how this relates to the regulation of their expression. Relationships between the synthesis of these unique oligosaccharide structures and their biological role in vivo will be determined using constructs that introduce the protein-specific beta1, 4GalNAcT recognition determinant into another protein. Characteristic of the protein-specific beta1, 4GalNAcT and the protein independent GalNAc-4- sulfoT will be defined at molecular level, by cloning these transferases and establishing how their structural features related to their ability to selectively modify oligosaccharides. The applicant will place particular emphasis on the developmental regulation of transferase expression. Understanding the selective modification of glycoproteins with specific oligosaccharide structures will provide important information on processes central to reproductive biology, as well as malignant transformation, inflammation, cell recognition, and protein targeting.

描述：N-连接寡糖以序列 S04- 结尾 4-GalNAc-beta1、4GlcNAc-beta (SGN) 在糖蛋白上是保守的 从鱼类到哺乳动物的脊椎动物的激素。这意味着 它们具有非常重要的功能，其定义是长期目标 申请人的研究。这些寡糖结构是 被 SGN 特异性受体识别，并在 例如，体内调节 LH 循环半衰期以最大化其 排卵周期期间受体激活。受到高度监管 这些结构的合成产生了一系列寡糖 含有由蛋白质起始的序列 GalNAc-beta1、4-GlcNAc-beta 选定糖蛋白上的特异性 beta1、4GalNAc 转移酶。三 随后添加 S04 可以产生不同的家族成员， 唾液酸或岩藻糖通过不依赖于蛋白质的转移酶如 GalNAc-4-磺基转移酶。该项目将追求两个主要具体目标 目标：1）。蛋白质调节的分子基础的定义- beta1 的特定且不依赖于蛋白质的糖基化形式， 4GalNAc-T 和 GalNAc-sulfoT 的体外和体内实验，以及 2)。 蛋白质特异性结构特征的分子定义 beta1、4GalNAc 转移酶和蛋白质独立的 GalNAc-4-sulfoT 解释其属性以及这与法规的关系 他们的表达。这些独特的合成之间的关系 寡糖结构及其在体内的生物学作用 使用引入蛋白质特异性β1的构建体确定， 4GalNAcT 识别决定簇成另一种蛋白质。特点 蛋白质特异性 beta1、4GalNAcT 和蛋白质非依赖性 GalNAc-4- sulfoT 将通过克隆这些转移酶在分子水平上进行定义 并确定它们的结构特征与它们的能力之间的关系 选择性修饰寡糖。 申请人将特别重视发展 转移酶表达的调节。了解选择性 用特定寡糖结构修饰糖蛋白 将提供有关生殖核心过程的重要信息 生物学，以及恶性转化、炎症、细胞 识别和蛋白质靶向。