GLYCOPROTEIN IN HORMONE OLIGOSACCHARIDES

激素低聚糖中的糖蛋白

• 批准号: 6380630
• 负责人: JACQUES U BAENZIGER
• 金额: $ 42.58万
• 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/6380630
• 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：以序列S 04-终止的N-连接寡糖 4-GalNAc-β 1，4GlcNAc-β（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，其定义是一个长期目标 申请人的研究。这些寡糖结构是 被SGN特异性受体识别，并在 体内，例如，在调节LH循环半衰期，以最大限度地提高其 排卵周期中的受体激活。受到高度监管的 这些结构的合成产生一个寡糖家族 含有由蛋白质起始的序列GalNAc-β 1，4-GlcNAc-β 特异性β 1，4GalNAc转移酶。三 不同的家族成员可以通过随后加入SO 4产生， 唾液酸或岩藻糖通过蛋白质非依赖性转移酶如 GalNAc-4-磺基转移酶。该项目将追求两个主要的具体 目的：1）.蛋白质调节的分子基础的定义- β 1的特异性和非蛋白质依赖性糖基化形式， 4GalNAc-T和GalNAc-sulfoT的体外和体内研究; 2）. 蛋白质特异性结构特征的分子定义 β 1，4 GalNAc转移酶和蛋白质非依赖性GalNAc-4-sulfoT 解释了它们的属性以及它们与监管的关系 他们的表情。这些独特的合成之间的关系 寡糖的结构和它们在体内的生物学作用， 使用引入蛋白特异性β 1的构建体测定， 4GalNAcT识别决定簇转化为另一种蛋白。特性 蛋白特异性β 1，4GalNAcT和蛋白非依赖性GalNAc-4- 通过克隆这些转移酶，将在分子水平上定义sulfoT 并确定它们的结构特征与它们的能力之间的关系， 选择性地修饰寡糖。 申请人将特别强调发展 转移酶表达的调节。理解选择性 具有特定寡糖结构的糖蛋白的修饰 将提供关于生殖健康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。