GLYCOSAMINOGLYCAN-PROTEIN INTERACTIONS IN MALARIA PARASITE INFECTION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 疟疾寄生虫恶性疟原虫被认为是通过VAR2CSA蛋白的某些结构域与细胞表面的糖胺聚糖相互作用，特别是软骨素4-硫酸盐(C4S)，导致孕妇感染的红细胞与胎盘结合。DBL3X结构域被预测在VAR2CSA与C4S的结合中发挥关键作用。Gowda博士的实验室已经提供了表达蛋白质DBLX3结构域的质粒和方案，以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低聚体，可用于评估相互作用的特异性，并将表达适当标记形式的蛋白质。核磁共振方法允许在排列的样品中使用13C化学位移各向异性偏移量来返回络合物的几何信息，这些方法源于之前由资源支持的关于剩余偶极耦合(RDC)的工作。

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).