NMR Studies of Biological Supramolecular Structures

University Of California San Diego, La Jolla CA

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Abstract

The overall goals of the research supported by this grant are to develop NMR methods for determining the structures of proteins in biological supramolecular structures, and to apply NMR spectroscopy to the study of filamentous bacteriophage coat proteins in membranes and virus particles, including those that display peptides on their surface. Experimental methods and instrumentation will be developed so that highresolution NMR data can be obtained from all backbone and side chain sites of proteins in biological supramolecular structures. This will enable NMR spectroscopy to be used to determine the complete three-dimensional atomic resolution structures of proteins in virus particles, membranes, and other biological supramolecular structures. The structures of the major coat proteins of several different filamentous bacteriophages will be determined by solid-state NMR experiments on completely aligned bacteriophage particles, and the structures of the membrane-bound forms of these proteins will be determined in weakly aligned micelles by solution NMR and in completely aligned bilayers by solid-state NMR. Comparisons between the viral and membrane-bound forms of the protein will give insight into the assembly process. NMR will also be used to determine the structures of peptide sequences inserted near the N-terminus of the major pVIII coat protein and displayed on the surface of filamentous bacteriophage particles. The same filamentous bacteriophage coat protein that is used to generate the peptide sequences also provides an ideal platform for determining the structures of the peptides by the solid-state NMR methods that we are developing. The peptide sequences under investigation extend the biological of the research to AIDS, malaria, influenza, and neurochemistry.