Support is requested to continue the development of solid-state NMR spectroscopy as a method for determining the structures of proteins and to make the instrumentation and methodology for solid-state NMR studies of proteins available to the biomedical research community by establishing a Research Resource in the Department of Chemistry at the University of Pennsylvania. This is an ideal location for a Resource, since the University is located in the center of the highest concentration of chemical and pharmaceutical research activity in the nation and the Department is in close proximity to the School of Medicine and the Wistar Institute. The technological research and development consists of the design, construction and optimization of instrumentation for high-field solid-state NMR spectroscopy and the development of new experimental methods for solid-state NMR spectroscopy; the development of NMR spectroscopy as a general method for determining the structures of peptides and proteins in membranes; and the application of solid-state NMR spectroscopy to the determination of the structures of peptides displayed on the surface of filamentous bacteriophages, the structure of vpu protein from HIV, and the structures of merP and merT proteins from the bacterial mercury detoxification system. A wide range of collaborative research projects are underway on: magainin antibiotic peptides (M. Zasloff), cecropin antibiotic peptides (B. Merrifield), channel forming peptides (M. Montal), tethered channel peptides (J. Tomich), model hydrophobic membrane peptides (L. Gierasch), colicins (W. Cramer), lung surfactant proteins SP- B and SP-C (J. Baatz), fusogenic peptides in membranes (W. DeGrado), subunit c of the F1F0 ATPase (R. Fillingame), NMDA receptor (M. Maccecchini), C60 in membranes (A. Smith), and protein-nucleic acid interactions (P. Lu). The instrumentation and staff will also be available in Service roles for a variety of projects. Training will occur through courses at the University, the participation of undergraduate, graduate, and postdoctoral students at the University in the research, and the participation of collaborators in their own research projects. Dissemination will occur through many mechanisms, starting with a brochure describing all of the facilities and activities of the resource, presentations at scientific meetings and workshops, and publications in scientific journals.
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| Marassi, F M; Ma, C; Gratkowski, H et al. (1999) Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1. Proc Natl Acad Sci U S A 96:14336-41 |
