CRYSTALLOGRAPHIC STUDIES OF CELL MIGRATION AND HOST-PATHOGEN INTERACTIONS

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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.