THE DEVELOPMENT AND APPLICATION OF COMPLEMENTARY STRUCTURAL TECHNIQUES

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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. At the Hauptman-Woodward Medical Research Institute (HWI) we have growing research areas in structural dynamics, protein complexes, and virus studies. In this proposal we request beamtime for collaborative studies between HWI staff and SSRL staff to develop three complementary areas of biological structural research. Specifically we have used complementary crystallographic and SAXS approaches to resolve dynamical aspects in tRNA recognition complexes. We will use a similar interdisciplinary SAXS and crystallographic approach to determine how different partners complex with the same protein and the affect on biological activity. This project requires synchrotron radiation to extend diffraction resolution and the detector facilities at SSRL to cope with large unit cells. We have a program of research on health-related issues caused by oxidative stress in the brain and lungs. Structural perturbations caused by x-ray irradiation are an important part of these studies. We are developing methods to flag radiation-induced structural changes to extrapolate back to the native structure. We require the use of synchrotron radiation to determine high-resolution detail to develop our radiation model. Finally, we are investigating viral interactions with the nuclear import pathway and developing technologies for high-throughput studies of whole viruses.