Consortia for High-Throughput-Enabled Structural Biology Partnerships

虽然结构生物学对于研究致病性分泌效应物是有力的，但还没有被用于大规模的研究。 以研究效应器-宿主蛋白质相互作用。在这个提议中，我们使用已知的和新的分泌的 效应器和实验管道，将提供广泛的见解如何一个模型病原体。 沙门氏菌，破坏宿主细胞功能。Aim 1同时提供了对效应器的关键功能见解 蛋白质的效力和功能，而在同一时间作为一个重要的 选择步骤，通过PSI网络将结构表征集中在最有价值的靶标上。目的2 提供了关于宿主蛋白质和蛋白质途径的有价值的信息，使用交联和 蛋白质组学，每个效应器相互作用，并提供PSI网络与主机的优先级列表 用于结构表征的蛋白质靶标。目的3询问可能的特异性蛋白质-蛋白质 相互作用，并提供了经验证的蛋白质-蛋白质相互作用和可能的配体的选择， PSI网络结构表征。最终，个体分泌的结构-功能研究 效应子对于宿主-病原体研究界是无价的。然而，对宿主-病原体的了解 从这种具有多个效应器的大规模并行表征工作中获得的生物学将 在更全面的系统层面上理解。

While powerful for studying pathogenic secreted effectors, structural biology has not been used to a large extent to study effector-host protein interactions. In this proposal, we use known and novel secreted effectors and an experimental pipeline that will provide broad insights into how a model pathogen. Salmonella, subverts host cell funcfion. Aim 1 simultaneously provides key functional insights into effector protein potency and funcfion using broad set of assays, while at the same fime serves as an important selection step to focus structural characterization by the PSI network on the most valuable targets. Aim 2 provides valuable information about the host proteins and protein pathways, using cross-linking and proteomics, that each effector interacts with and provides the PSI network with a prioritized list of host protein targets for structural characterization. Aim 3 interrogates possible specific protein-protein interactions and provides a selection of validated protein-protein interactions and possibly ligands for structural characterizafion by PSI network. Ultimately, structure-funcfion studies of individual secreted effectors are invaluable to the host-pathogen research community. However, the insights into host-pathogen biology gained from this large parallel characterizafion effort with multiple effectors will advance understanding at a more complete systems level.