CRYSTALLOGRAPHIC STUDIES OF CELL MIGRATION AND HOST-PATHOGEN INTERACTIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 SSRL仍然是我们获得大分子同步加速器束线的首选。我们的主要需求是MAD相位的可调性，从大型单元单元收集数据的高亮度，以及毒素抑制剂复合体的相对高通量数据收集。我们的工作涵盖了广泛的蛋白质靶标，重点放在两个领域：(1)CDC A-C类病原体的关键毒力因子，以及它们与宿主蛋白质和抗体的复合体，以及这些相互作用的小分子抑制剂，以促进药物设计；(2)控制细胞迁移的主要蛋白质及其蛋白质-蛋白质和蛋白质-脂质相互作用。其中一些蛋白质很大，它们的单位细胞必然很大，需要高亮度的光源来收集高分辨率的数据。对于中等大小的蛋白质，如炭疽致死因子，SR对于收集足够分辨率的数据以合理药物设计的目的起着关键的作用。在其他情况下，具有合理亮度的可调谐光源对于从头算相位是足够的。在过去的6年里，SSRL收集的数据对该实验室20多个新晶体结构的结构确定至关重要，导致23篇论文发表在国际期刊上。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The SSRL continues to be our first choice for access to macromolecular synchrotron beam-lines. Our principal needs are tunability for MAD phasing, high brightness for data collection from large unit cells, and relatively high-throughput data collection for toxin-inhibitor complexes. Our work covers a broad range of protein targets, with an emphasis in two areas: (1) key virulence factors from CDC Category A-C pathogens, and their complexes with host proteins and antibodies, as well as small molecule inhibitors of these interactions to facilitate drug design; and (2) the major proteins and their protein-protein and protein-lipid interactions that control cell migration. Some of these proteins are large, and their necessarily large unit cells demand a high brightness source for high resolution data collection. For proteins in the medium-sized range, such as anthrax lethal factor, SR makes the key difference for collecting data of sufficient resolution for the purpose of rational drug design. In other cases, a tunable source with reasonable brightness is sufficient for ab initio phasing. Over the past 6 years, data collected at the SSRL have been critical for the structure determination of more than 20 novel crystal structures from this laboratory, leading to 23 papers published in international journals.