This is the competitive renewal application for the grant that supports the Resource for NMR Molecular Imaging of Proteins at the University of California, San Diego. The Resource develops and applies NMR spectroscopy for the study of proteins in biological supramolecular structures, with most of the effort focused on developing a method for determining the three-dimensional structures of membrane proteins in phospholipid bilayers. As a P41-grant supported Research Resource, there are five components to the research program. (1) Core technological research and development is focused on solid-state NMR of proteins, and involves the development of instrumentation, largely the design and construction of new coils and probes;experimental methods, largely new pulse sequences;sample preparation starting with the expression of isotopically labeled proteins;and structure calculations. (2) Collaborative research is divided into two categories to reflect their impact on the Core. The Central Collaborations include structure determinations of the viroporins Vpu from HIV-1 and p7 from HCV, mercury transport membrane proteins with two, three, and four trans-membrane helices, filamentous bacteriophage coat proteins, and GPCRs (Gprotein coupled receptors). The studies of GPCRs are performed in the context of a Bioengineering Research Partnership, which relies on the Resource for its technology base. There are many Remote Collaborations with groups at other institutions interested in utilizing the Resource to study a wide variety of membrane proteins, ranging in complexity from antibiotic peptides to rhodopsin. (3) Service activities are in the areas of instrumentation development and access to the high field NMR spectrometers by expert users. (4) Training is performed continuously because many aspects of the technology are unique to the Resource. (5) Dissemination results from publications, the web site, and many email and telephone requests for specific information. We also work with the major vendors of NMR instrumentation to promote the spread of the technology developed at the Resource.
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