CRYSTALLOGRAPHIC STUDIES OF CELL MIGRATION AND HOST-PATHOGEN INTERACTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 SSRL仍然是我们获得大分子同步加速器光束线的首选。我们的主要需求是MAD定相的可调谐性，从大单元电池收集数据的高亮度，以及毒素抑制剂复合物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点，重点是两个领域：（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物，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。这些蛋白质中的一些是大的，并且它们的必要的大单位细胞需要高亮度源以用于高分辨率数据收集。对于中等大小的蛋白质，如炭疽致死因子，SR在收集足够分辨率的数据以进行合理药物设计方面发挥了关键作用。在其他情况下，具有合理亮度的可调谐源足以用于从头算定相。在过去的6年里，在SSRL收集的数据对该实验室的20多个新晶体结构的结构测定至关重要，导致23篇论文在国际期刊上发表。

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.