Ultra-High Resolution Structure and Dynamics of Bilayer Bound Polypeptides

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9317111 Cross Dr. Cross will continue the development of solid state NMR spectroscopy for the determination of macromolecular structure and dynamics in samples experiencing an anisotropic environment. The efforts here focus on peptides bound in lipid bilayers where the global motions are restricted to the axial rotation about the bilayer normal. Local motions will be characterized in detail and a thorough investigation of correlated motions that may extend beyond the peptide into its environment will be sought. Very high resolution structural information will be obtained from orientational constraints which have already been shown to have a very level of accuracy. Through such a dynamic and structural characterization it is hoped that a more detailed view of the potential energy surfaces of the polypeptide backbone can be achieved. Furthermore, correlations between dynamic rates and kinetic rates may lead to unprecedented descriptions of relationships between structure dynamics and function. To achieve these goals a variety of solid state NMR techniques will be refined and combined with unique sample preparation schemes that both orient lipid bilayers and their host peptides as well as specific site isotopically labeled molecules. %%% The development of methods for the determination of macromolecular structure for those proteins and other molecules that are not easily studied by the more traditional methods, such as x ray diffraction will be continued. The approach taken here will utilize Nuclear Resonance spectroscopy of samples that have one dimensional order, such as an oriented film. In this way all molecules are aligned with respect to the magnetic field of the instrument and structural constraints are readily achieved. Membrane bound proteins are a very important class of biological macromolecules that are responsible for much of the communication between cells in living tissue. For x ray diffraction it has been very difficult to form cocrystals of these proteins and the lipid molecules that make up their membrane environment. However, it has been possible to form uniformly aligned samples for the NMR spectroscopy and therefore, this method is expected to play a very important role in the structure determination of this important class of proteins. ***