ISOTOPE LABELING OF GLYCOPROTEIN GLYCANS FOR NMR OBSERVATION

用于 NMR 观察的糖蛋白聚糖的同位素标记

• 批准号: 8361810
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361810
• 关键词: Arthritis; Binding; Binding Proteins; Binding Sites; Blood Vessels; Chondroitin Sulfates; Extracellular Matrix; Funding; Genes; Glycoproteins; Glycosaminoglycans; Grant; Heparitin Sulfate; Hyaluronan; Isotope Labeling; Link; National Center for Research Resources; Plasmids; Polysaccharides; Principal Investigator; Process; Research; Research Infrastructure; Resources; Rheumatoid Arthritis; Source; Structure; System; Tumor Necrosis Factor-alpha; United States National Institutes of Health; cost; professor; response to injury

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. TSG-6, the secreted product of tumor necrosis factor-stimulated gene-6, is composed of a Link module and a CUB module domain. The Link module is involved in binding to glycosaminoglycans and the entire system is in someway involved in remodeling the extracellular matrix. This is a process that normally occurs in response to injury of blood vessels but also occurs in rheumatoid arthritis and osteo-arthritis. The particular glycosaminoglycans to which the TSG-6 Link module binds include hyaluronan, heparan sulfate and chondroitin sulfate, but it appears that the binding sites might be different and interact allosterically. Professor Day has supplied the plasmid and expression advice on this glycosaminoglycan-binding protein. The Resource is providing the chondroitin sulfate oligomers and the NMR expertise to structurally define the binding mode. The project will use specialized orientational constraints developed in the Resource to facilitate structure determination.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 TSG-6是肿瘤坏死因子刺激基因6的分泌产物，由Link模块和CUB模块结构域组成。 Link 模块参与与糖胺聚糖的结合，整个系统以某种方式参与细胞外基质的重塑。 这是一个通常因血管损伤而发生的过程，但也发生在类风湿性关节炎和骨关节炎中。 TSG-6 Link 模块结合的特定糖胺聚糖包括透明质酸、硫酸乙酰肝素和硫酸软骨素，但结合位点似乎可能不同并以变构方式相互作用。 Day 教授提供了有关这种糖胺聚糖结合的质粒和表达建议 蛋白质。 该资源提供硫酸软骨素低聚物和 NMR 专业知识，以从结构上定义结合模式。 该项目将使用资源中开发的专门方向约束来促进结构确定。