GLYCOSAMINOGLYCAN-PROTEIN INTERACTIONS IN MALARIA PARASITE INFECTION

疟疾寄生虫感染中的糖胺聚糖-蛋白质相互作用

• 批准号: 8361799
• 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/8361799
• 关键词: Anisotropy; Binding; Cell surface; Chemicals; Chondroitin Sulfate A; Complex; Erythrocytes; Funding; Glycosaminoglycans; Grant; Human Resources; Infection; Label; Laboratories; Malaria; Methods; National Center for Research Resources; Parasites; Placenta; Plasmids; Plasmodium falciparum; Play; Pregnant Women; Principal Investigator; Proteins; Protocols documentation; Research; Research Infrastructure; Residual state; Resources; Sampling; Source; Specificity; Tertiary Protein Structure; Testing; United States National Institutes of Health; Work; cost; stem

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. The malaria parasite, Plasmodium falciparum, is believed to cause binding of infected erythrocytes to the placenta in pregnant women through interactions of certain domains of the VAR2CSA protein with cell-surface glycosaminoglycans, specifically chondroitin 4-sulfate (C4S). DBL3X domain has been predicted to play key roles in the binding of VAR2CSA to C4S. Dr Gowda's laboratory has provided plasmids and protocols for expressing the DBLX3 domain of the protein for the purpose of testing and characterizing these hypothesized interactions. Personnel at the Resource are producing 13C-labeled forms of specific C4S oligomers that can be used in assessing the specificity of interactions and will express appropriately labeled forms of the protein. The NMR methods that allow use of 13C chemical shift anisotropy offsets in aligned samples to return geometry information on the complexes stem from pre8vious Resource supported work on residual dipolar couplings (RDCs).

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 并且子项目的首席研究员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。 据信，疟原虫恶性疟原虫通过 VAR2CSA 蛋白的某些结构域与细胞表面糖胺聚糖（特别是 4-硫酸软骨素 (C4S)）的相互作用，导致受感染的红细胞与孕妇的胎盘结合。 据预测，DBL3X 结构域在 VAR2CSA 与 C4S 的结合中发挥关键作用。 Gowda 博士的实验室提供了表达该蛋白质 DBLX3 结构域的质粒和方案，用于测试和表征这些假设的相互作用。 该资源的工作人员正在生产 13C 标记形式的特定 C4S 寡聚物，可用于评估相互作用的特异性，并表达适当标记形式的蛋白质。 NMR 方法允许在对齐的样品中使用 13C 化学位移各向异性偏移来返回复合物的几何信息，该方法源于先前资源支持的残余偶极耦合 (RDC) 工作。