Structural studies of proteins by paramagnetic solid-state NMR spectroscopy

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In this project the PI is developing new multidimensional NMR spectroscopy techniques for the determination of three-dimensional protein structures in the solid phase. These NMR methods rely on the use of covalently-attached paramagnetic tags and exploit the large electron-nucleus hyperfine interactions to simultaneously obtain long, up to ~20 Å, electron-nucleus distance restraints at multiple protein sites. The principal research objectives of the project are: to develop methodology for the collection of paramagnetic-based NMR structural restraints with enhanced sensitivity, to develop methodology for probing the higher order intermolecular architecture of large protein assemblies, and to design compact paramagnetic tags to improve the quality of protein structures derived using this methodology. The paramagnetic solid-state NMR techniques emerging from this project are expected to be directly applicable to the structural analysis of a variety of large macromolecular assemblies that are central to fundamental biological processes yet do not readily lend themselves to characterization using traditional high-resolution structural tools.The research aims of the project are integrated with education and outreach activities. The primary educational activity will consist of intensive, full-time summer research internship programs for undergraduate and local high-school students organized annually in the PI's laboratory. Student recruitment for these programs will focus particularly on students from groups traditionally under-represented in the STEM disciplines. The main objective of these activities is to directly impact students in the earliest stages of their educational experience by introducing them to cutting edge interdisciplinary research at the interface of chemistry, biology, and physics, building their confidence in themselves and their scientific abilities, and encouraging them to think of science in a broad, discovery-based manner. The ultimate goal is to increase student participation and retention in the STEM fields. This project is jointly supported by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences and by the Chemistry of Life Processes Program in the Chemistry Division.